Protein carbonylation

The region-specific mechanical function of left ventricular (LV) murine cardiomyocytes and the role of phosphorylation and oxidative modifications of myofilament proteins were investigated in the process of post-myocardial infarction (MI) remodelling 10 weeks after ligation of the left anterior descending (LAD) coronary artery. Permeabilized murine cardiomyocytes from the remaining anterior and a remote non-infarcted inferior LV area were compared with those of non-infarcted age-matched controls. Myofilament phosphorylation, sulfhydryl (SH) oxidation, and carbonylation were also assayed. Ca 2+ sensitivity of force production was significantly lower in the anterior wall (pCa 50 : 5.81 + 0.03, means + SEM, at 2.3 mm sarcomere length) than that in the controls (pCa 50 : 5.91 + 0.02) or in the MI inferior area (pCa 50 : 5.88 + 0.02). The level of troponin I phosphorylation was lower and that of myofilament protein SH oxidation was higher in the anterior location relative to controls, but these changes did not explain the differences in Ca 2+ sensitivities. On the other hand, significantly higher carbonylation levels, [e.g. in myosin heavy chain (MHC) and actin] were observed in the MI anterior wall [carbonylation index (CI), CI MHC : 2.06 + 0.46, CI actin : 1.46 + 0.18] than in the controls (CI: 1). In vitro Fenton-based myofilament carbonylation in the control cardiomyocytes also decreased the Ca 2+ sensitivity of force production irrespective of the phosphorylation status of the myofilaments. Furthermore, the Ca 2+ sensitivity correlated strongly with myofilament carbonylation levels in all investigated samples. Post-MI myocardial remodelling involves increased myofibrillar protein carbonylation and decreased Ca 2+ sensitivity of force production, leading potentially to contractile dysfunction in the remaining cardiomyocytes of the infarcted area.

Use of wireless communicating devices is increasing at an exponential rate in present time and is raising serious concerns about possible adverse effects of microwave (MW) radiation emitted from these devices on human health. The present study aimed to evaluate the effects of 900 MHz MW radiation exposure on cognitive function and oxidative stress in blood of Fischer rats. Animals were divided into two groups (6 animals/group): Group I (MW-exposed) and Group II (Sham-exposed). Animals were subjected to MW exposure (Frequency 900 MHz; specific absorption rate 8.4738 x 10(-5) W/kg) in Gigahertz transverse electromagnetic cell (GTEM) for 30 days (2 h/day, 5 days/week). Subsequently, cognitive function and oxidative stress parameters were examined for each group. Results showed significant impairment in cognitive function and increase in oxidative stress, as evidenced by the increase in levels of MDA (a marker of lipid peroxidation) and protein carbonyl (a marker of protein oxidation) a...

Background: Detachment of photoreceptors from the underlying retinal pigment epithelium is seen in various retinal disorders such as retinal detachment and age-related macular degeneration and leads to loss of photoreceptors and vision. Pharmacologic inhibition of photoreceptor cell death may prevent this outcome. This study tests whether systemic administration of tauroursodeoxycholic acid (TUDCA) can protect photoreceptors from cell death after experimental retinal detachment in rodents. Methodology/Principal Findings: Retinal detachment was created in rats by subretinal injection of hyaluronic acid. The animals were treated daily with vehicle or TUDCA (500 mg/kg). TUNEL staining was used to evaluate cell death. Photoreceptor loss was evaluated by measuring the relative thickness of the outer nuclear layer (ONL). Macrophage recruitment, oxidative stress, cytokine levels, and caspase levels were also quantified. Three days after detachment, TUDCA decreased the number of TUNEL-positive cells compared to vehicle (651668/mm 2 vs. 1314668/mm 2 , P = 0.001) and prevented the reduction of ONL thickness ratio (0.8460.03 vs. 0.6560.03, P = 0.002). Similar results were obtained after 5 days of retinal detachment. Macrophage recruitment and expression levels of TNF-a and MCP-1 after retinal detachment were not affected by TUDCA treatment, whereas increases in activity of caspases 3 and 9 as well as carbonyl-protein adducts were almost completely inhibited by TUDCA treatment. Conclusions/Significance: Systemic administration of TUDCA preserved photoreceptors after retinal detachment, and was associated with decreased oxidative stress and caspase activity. TUDCA may be used as a novel therapeutic agent for preventing vision loss in diseases that are characterized by photoreceptor detachment.

Free radicals generated in a variety of biological systems have been implicated in mechanisms of aging and age-related pathologies. This study strategically revealed the varying levels of carbonylated proteins in 3 different tissues of 40 wistar rats of varying ages. Their ages include 25-30, 45-50 and 65-70 days. The brain, heart and kidney tissue homogenates were prepared and biochemically analyzed for products of protein oxidation using 2,4-dinitrophenylhydrazones and autoantibodies against carbonylated proteins. This study revealed a direct proportional relationship between age and protein carbonylation in brain, heart and kidney tissue homogenates. The level of carbonylated proteins were significantly (P≤0.05) increased in the assayed tissues as all test groups advanced in age. Oxidative modification of proteins in brain and kidney tissues showed

Background/aim-Age-related metabolic diseases are often associated with low-grade inflammation. The aim of the present study was to investigate the role of the transcriptional coactivator PGC-1α in the potential beneficial effects of exercise training and/or resveratrol in the prevention of age-associated low-grade inflammation. To address this, a long-term voluntary exercise training and resveratrol supplementation study was conducted. Experimental setup-Three month old whole body PGC-1α KO and WT mice were randomly assigned to four groups: untrained chow-fed, untrained chow-fed supplemented with resveratrol, chow-fed voluntarily exercise trained and chow-fed supplemented with resveratrol and voluntarily exercise trained. The intervention lasted 12 months and three month old untrained chow-fed mice served as young controls. Results-Voluntary exercise training prevented an age-associated increase (p<0.05) in systemic IL-6 and adiposity in WT mice. PGC-1α expression was required for a training-induced prevention of an age-associated increase (p<0.05) in skeletal muscle TNFα protein. Independently of PGC-1α, both exercise training and resveratrol prevented an age-associated increase (p<0.05) in skeletal muscle protein carbonylation. The present findings highlight that exercise training is a more effective intervention than resveratrol supplementation in reducing age-associated inflammation and that PGC-1α in part is required for the exercise training-induced anti-inflammatory effects.

Immobilization induces oxidative damage to the brain. Ilex paraguariensis extracts (Mate) and chlorogenic acid (CGA), its major natural compound, exert protective effects against reactive oxygen species (ROS) formation. Here, the effects of Mate and CGA on oxidative damage induced by chronic immobilization stress (CIS) in cortex (CTX), hippocampus (HIP) and striatum (STR) were investigated. For CIS, animals were immobilized during 6 h every day for 21 consecutive days. Rats received Mate or CGA daily by intra-gastric gavage 30 min before every restraint session. Endpoints of oxidative stress (levels of lipid peroxidation, protein carbonylation, and reduced (GSH) and oxidized (GSSG) forms of glutathione) were evaluated following CIS. While CIS increased oxidized lipids and carbonyl levels in all brain regions, CGA (and Mate in a lesser extent) attenuated lipid and protein oxidation as compared to control groups. GSH/GSSG balance showed a tendency to increase in all regions in respons...

Elevated mitochondrial reactive oxygen species have been suggested to play a causative role in some forms of muscle insulin resistance. However, the extent of their involvement in the development of diet-induced insulin resistance remains unclear. To investigate, manganese superoxide dismutase (MnSOD), a key mitochondrial-specific enzyme with antioxidant modality, was overexpressed, and the effect on in vivo muscle insulin resistance induced by a high-fat (HF) diet in rats was evaluated. Male Wistar rats were maintained on chow or HF diet. After 3 wk, in vivo electroporation (IVE) of MnSOD expression and empty vectors was undertaken in right and left tibialis cranialis (TC) muscles, respectively. After one more week, insulin action was evaluated using hyperinsulinemic euglycemic clamp, and tissues were subsequently analyzed for antioxidant enzyme capacity and markers of oxidative stress. MnSOD mRNA was overexpressed 4.5-fold, and protein levels were increased by 70%, with protein de...

BACKGROUND AND PURPOSE3,4‐Methylenedioxymethamphetamine (MDMA or ‘Ecstasy’) is a worldwide major drug of abuse known to elicit neurotoxic effects. The mechanisms underlying the neurotoxic effects of MDMA are not clear at present, but the metabolism of dopamine and 5‐HT by monoamine oxidase (MAO), as well as the hepatic biotransformation of MDMA into pro‐oxidant reactive metabolites is thought to contribute to its adverse effects.EXPERIMENTAL APPROACHUsing mouse brain synaptosomes, we evaluated the pro‐oxidant effects of MDMA and its metabolites, α‐methyldopamine (α‐MeDA), N‐methyl‐α‐methyldopamine (N‐Me‐α‐MeDA) and 5‐(glutathion‐S‐yl)‐α‐methyldopamine [5‐(GSH)‐α‐MeDA], as well as those of 5‐HT, dopamine, l‐DOPA and 3,4‐dihydroxyphenylacetic acid (DOPAC).KEY RESULTS5‐HT, dopamine, l‐DOPA, DOPAC and MDMA metabolites α‐MeDA, N‐Me‐α‐MeDA and 5‐(GSH)‐α‐MeDA, concentration‐ and time‐dependently increased H2O2 production, which was significantly reduced by the antioxidants N‐acetyl‐l‐cyste...

Atherosclerosis and valvular heart disease often require treatment with corrective surgery to prevent future myocardial infarction, ischemic heart disease, and heart failure. Mechanisms underlying the development of the associated complications of surgery are multifactorial and have been linked to inflammation and oxidative stress, classically as measured in the blood or plasma of patients. Postoperative pericardial fluid (PO-PCF) has not been investigated in depth with respect to the potential to induce oxidative stress. This is important because cardiac surgery disrupts the integrity of the pericardial membrane surrounding the heart and causes significant alterations in the composition of the pericardial fluid (PCF). This includes contamination with hemolyzed blood and high concentrations of oxidized hemoglobin, which suggests that cardiac surgery results in oxidative stress within the pericardial space. Accordingly, we tested the hypothesis that PO-PCF is highly pro-oxidant and that the potential interaction between inflammatory cell-derived hydrogen peroxide with hemoglobin is associated with oxidative stress. Blood and PCF were collected from 31 patients at the time of surgery and postoperatively from 4 to 48 h after coronary artery bypass grafting, valve replacement, or valve repair (mitral or aortic). PO-PCF contained high concentrations of neutrophils and monocytes, which are capable of generating elevated amounts of superoxide and hydrogen peroxide through the oxidative burst. In addition, PO-PCF primed naive neutrophils resulting in an enhanced oxidative burst upon stimulation. The PO-PCF also contained increased concentrations of cell-free oxidized hemoglobin that was associated with elevated levels of F 2a isoprostanes and prostaglandins, consistent with both oxidative stress and activation of cyclooxygenase. Lastly, protein analysis of the PO-PCF revealed evidence of protein thiol oxidation and protein carbonylation. We conclude that PO-PCF is highly pro-oxidant and speculate that it may contribute to the risk of postoperative complications.

Background.Increased oxidative stress is a well described feature of patients in hemodialysis. Their need for multiple blood transfusions and supplemental iron causes a significant iron overload that has recently been associated with increased oxidation of polyunsaturated lipids and accelerated aging due to DNA damage caused by telomere shortening.Methods.A total of 70 patients were evaluated concomitantly, 35 volunteers with ferritin levels below 500 ng/mL (Group A) and 35 volunteers with ferritin levels higher than 500 ng/mL (Group B). A sample of venous blood was taken to extract DNA from leukocytes and to measure relative telomere length by real-time PCR.Results.Patients in Group B had significantly higher plasma TBARS (p=0.008), carbonyls (p=0.0004), and urea (p=0.02) compared with those in Group A. Telomeres were significantly shorter in Group B, 0.66 (SD, 0.051), compared with 0.75 (SD, 0.155) in Group A (p=0.0017). We observed a statistically significant association between ...

Oxidative stress adaptation or hormesis is an important mechanism by which cells and organisms respond to, and cope with, environmental and physiological shifts in the level of oxidative stress. Most studies of oxidative stress adaption have been limited to adaptation induced by acute stress. In contrast, many if not most environmental and physiological stresses are either repeated or chronic. In this study we find that both cultured mammalian cells, and the fruit fly Drosophila melanogaster, are capable of adapting to chronic or repeated stress by up-regulating protective systems, such as their proteasomal proteolytic capacity to remove oxidized proteins. Repeated stress adaptation resulted in significant extension of adaptive responses. Repeated stresses must occur at sufficiently long intervals, however (12 hours or more for MEF cells and 7 days or more for flies), for adaptation to be successful, and the level of both repeated and chronic stress must be lower than is optimal for adaptation to acute stress. Regrettably, regimens of adaptation to both repeated and chronic stress that were successful for short-term survival in Drosophila, nevertheless also caused significant reductions in lifespan for the flies. Thus, although both repeated and chronic stress can be tolerated, they may result in a shorter life.

Hyperglycemia-associated oxidative stress leads to various pathophysiological complications in diabetes mellitus. Here, the effects of Glycyrrhiza glabra (G. glabra) root extract of streptozotocin (STZ)-induced diabetic changes and the associated free iron-mediated oxidative reactions were investigated. The animals were divided into five group, Group 1: Control (NC received buffer); Group 2: STZ-induced (DC); Group

Recent studies have shown benefits for the supplementation of folic acid in schizophrenic patients. The aim of this study was to evaluate the effects of folic acid addition on adult rats, over a period of 7 or 14 days. It also sets out to verify any potential protective action using an animal model of schizophrenia induced by ketamine, in behavioral and biochemical parameters. This study used two protocols (acute and chronic) for the administration of ketamine at a dose of 25 mg/kg (i.p.). The folic acid was given by oral route in doses of 5, 10 and 50 mg/kg, once daily, for 7 and/or 14 days in order to compare the protective effects of folic acid. Thirty minutes after the last administration of ketamine, the locomotor and social interaction activities were evaluated, and immediately the brain structure were removed for biochemical analysis. In this study, ketamine was administered in a single dose or in doses over the course of 7 days increasing the animal&#39;s locomotion. This st...

Inanga (Galaxias maculatus) are a euryhaline and amphidromous Southern hemisphere fish species inhabiting waters highly contaminated in trace elements such as nickel (Ni). Ni is known to exert its toxic effects on aquatic biota via three key mechanisms: inhibition of respiration, impaired ion regulation, and stimulation of oxidative stress. Inanga acclimated to freshwater (FW), 50% seawater (SW) or 100% SW were exposed to 0, 150 or 2000 μg Ni L(-1), and tissue Ni accumulation, metabolic rate, ion regulation (tissue ions, calcium (Ca) ion influx), and oxidative stress (catalase activity, protein carbonylation) were measured after 96 h. Ni accumulation increased with Ni exposure concentration in gill, gut and remaining body, but not in liver. Only in the gill was Ni accumulation affected by exposure salinity, with lower branchial Ni burdens in 100% and 50% SW inanga, relative to FW fish. There were no Ni-dependent effects on respiration, or Ca influx, and the only Ni-dependent effect ...

1) Background: Mucilage within cacao pods contains high levels of polyphenols. We investigated whether consumption of cacao juice enhances the recovery of muscle function following intensive knee extension exercise. (2) Methods: Ten recreationally active males completed two trials of 10 sets of 10 single leg knee extensions at ~80% one repetition maximum. Participants consumed each supplement (ZumoCacao ® juice, CJ or a dextrose drink, PL) for 7 days prior to and 48 h post exercise. Knee extension maximum voluntary contraction (MVC) and a counter movement jump (CMJ) were performed at baseline, immediately, 24 h, and 48 h post-exercise. Venous blood samples were collected at each time point and analyzed for indices of inflammation, oxidative damage, and muscle damage. (3) Results: CMJ height recovered faster with CJ at 24 h and 48 h post-exercise (p < 0.05), but there was no effect of CJ on recovery of MVC (both p > 0.05). There was also no effect of the trial on any blood markers (all p > 0.05). (4) Conclusions: Supplementation with CJ for 7 days prior to and 2 days after intensive knee extensor exercise improved functional recovery as shown by an improved recovery of CMJ up to 48 h post-exercise. However, the precise mechanism of action is unclear and requires further investigation.

1) Background: Mucilage within cacao pods contains high levels of polyphenols. We investigated whether consumption of cacao juice enhances the recovery of muscle function following intensive knee extension exercise. (2) Methods: Ten recreationally active males completed two trials of 10 sets of 10 single leg knee extensions at ~80% one repetition maximum. Participants consumed each supplement (ZumoCacao ® juice, CJ or a dextrose drink, PL) for 7 days prior to and 48 h post exercise. Knee extension maximum voluntary contraction (MVC) and a counter movement jump (CMJ) were performed at baseline, immediately, 24 h, and 48 h post-exercise. Venous blood samples were collected at each time point and analyzed for indices of inflammation, oxidative damage, and muscle damage. (3) Results: CMJ height recovered faster with CJ at 24 h and 48 h post-exercise (p < 0.05), but there was no effect of CJ on recovery of MVC (both p > 0.05). There was also no effect of the trial on any blood markers (all p > 0.05). (4) Conclusions: Supplementation with CJ for 7 days prior to and 2 days after intensive knee extensor exercise improved functional recovery as shown by an improved recovery of CMJ up to 48 h post-exercise. However, the precise mechanism of action is unclear and requires further investigation.

Chronic respiratory diseases such as obstructive pulmonary disease (COPD) and oxidative stress may underlie lung cancer (LC). We hypothesized that the profile of oxidative and antioxidant events may differ in lung tumors and blood compartments of patients with non-small cell LC (NSCLC) with and without COPD. Redox markers were analyzed (immunoblotting, ELISA, chemiluminescence, 2D electrophoresis, and proteomics) in blood samples of 17 control subjects and 80 LC patients (LC-COPD, 59 and LC, 21) and lung specimens (tumor and non-tumor) from those undergoing thoracotomy (35, LC-COPD, 23 and LC, 12). As smoking history was more prevalent in LC-COPD patients, these were further analyzed post-hoc as heavy and moderate smokers (cut-off, 60 packs-year). MDA-protein adducts and SOD1 levels were higher in tumor and non-tumor samples of LC-COPD than in LC. In tumors compared to non-tumors, SOD2 protein content was greater, whereas catalase levels were decreased in both LC and LC-COPD patient...

Cigarette smoking has been associated with high risk of neurological diseases such as stroke, Alzheimer's disease, multiple sclerosis, etc., The present study was designed to evaluate the restorative effects of Sesbania grandiflora (S. grandiflora) on oxidative damage induced by cigarette smoke exposure in the brain of rats. Adult male Wistar-Kyoto rats were exposed to cigarette smoke for a period of 90 days and consecutively treated with S. grandiflora aqueous suspension (SGAS, 1000 mg/kg body weight per day by oral gavage) for a period of 3 weeks. The levels of protein carbonyl, nitric oxide, and activities of cytochrome P450, NADPH oxidase and xanthine oxidase were significantly increased, whereas the levels of total thiol, protein thiol, non-protein thiol, nucleic acids, tissue protein and the activities of Na + / K + -ATPase, Ca 2+ -ATPase and Mg 2+ -ATPase were significantly diminished in the brain of rats exposed to cigarette smoke as compared with control rats. Also cigarette smoke exposure resulted in a significant alteration in brain total lipid, total cholesterol, triglycerides and phospholipids content. Treatment of SGAS is regressed these alterations induced by cigarette smoke. The results of our study suggest that S. grandiflora restores the brain from cigarette smoke induced oxidative damage. S. grandiflora could have rendered protection to the brain by stabilizing their cell membranes and prevented the protein oxidation, probably through its free radical scavenging and anti-peroxidative effect.

IntroductionThe purpose of this study was to: (i) investigate the effect of six months of resistance training (RT) on body composition, muscle strength, hematological patterns, and redox profile in maintenance hemodialysis (HD) patients, and; (ii) evaluate the effects of baseline concentrations of hemoglobin on the RT response.MethodsOne hundred fifty-seven subjects with chronic kidney disease (CKD) were randomly allocated into two groups: Control [CTL, (n = 76)] and RT (n = 81). A first visit was required for anamnesis and anthropometric measurements. Venous blood samples were collected at baseline and after twenty-four weeks of training in all patients for the analysis of clinical and redox balance markers. The RT program spanned six months and consisted of three sets of 8–12 repetitions with a rating of perceived exertion between 5 and 8 for three weekly sessions. Each exercise session was performed in twelve resistance exercises and it least for approximately 40 min.ResultsThe m...

Inflammatory status is observed in patients with chronic renal failure (CRF). The relationship between oxygen free radical production and dialysis could play an important role in protein oxidation. Carbonyl protein plasma level is an important tool in the study of protein stress, and it is related to the arterial intima thickness in the atherosclerosis process. We studied protein oxidative stress in 21 peritoneal dialysis (PD) patients and 42 hemodialysis (HD) patients as compared with 32 undialyzed patients with CRF. Carbonyl protein plasma levels were measured in nanomoles per milligram protein by the ELISA method (Winterbourn et al). Dialysis patients had a higher protein carbonyl content than did CRF patients (0.1265 +/- 0.04 nmol/mg vs. 0.1594 +/- 0.03 nmol/mg, p &lt; 0.0002). Patients on PD had a lower level than patients on HD (0.1452 +/- 0.03 nmol/mg vs. 0.1665 +/- 0.04, p &lt; 0.004). Glucose administration in PD is known to be able to increase glucose degradation products ...

SummaryReactive oxygen and nitrogen species are involved in a plethora of cellular responses in plants; however, our knowledge on the outcomes of oxidative and nitrosative signaling is still unclear. To better understand how oxidative and nitrosative signals are integrated to regulate cellular adjustments to external conditions, local and systemic responses were investigated in the roots and leaves of sour orange plants (Citrus aurantium L.) after root treatment with hydrogen peroxide (H2O2) or sodium nitroprusside (a nitric oxide donor), followed by NaCl stress for 8 days. Phenotypic and physiological data showed that pre‐exposure to these treatments induced an acclimation to subsequent salinity stress that was accompanied by both local and systemic H2O2 and nitric oxide (NO) accumulation. Combined histochemical and fluorescent probe approaches showed the existence of a vascular‐driven long‐distance reactive oxygen species and NO signaling pathway. Transcriptional analysis of genes...

Increased cellular levels of reactive oxygen species are known to occur during seed development and germination, but the consequences in terms of protein degradation are poorly characterized. In this work, protein carbonylation, which is an irreversible oxidation process leading to a loss of function of the modified proteins, has been analyzed by a proteomic approach during the first stages of Arabidopsis (Arabidopsis thaliana) seed germination. In the dry mature seeds, the legumin-type globulins (12S cruciferins) were the major targets. However, the acidic α-cruciferin subunits were carbonylated to a much higher extent than the basic (β) ones, consistent with a model in which the β-subunits are buried within the cruciferin molecules and the α-subunits are more exposed to the outside. During imbibition, various carbonylated proteins accumulated. This oxidation damage was not evenly distributed among seed proteins and targeted specific proteins as glycolytic enzymes, mitochondrial AT...

Hydrogen peroxide (H 2 O 2 ) and nitric oxide ( • NO) elicit numerous processes in plants. However, our knowledge of H 2 O 2 and • NO-responsive proteins is limited. The present study aimed to identify proteins whose accumulation levels were regulated by these signaling molecules in citrus leaves. To address this question, hydroponically grown citrus plants were treated by incubating their roots in the presence of H 2 O 2 or the • NO donor, sodium nitroprusside (SNP). Both treatments induced H 2 O 2 and • NO production in leaves, indicating occurrence of oxidative and nitrosative stress conditions. However, treated plants maintained their normal physiological status. The vascular system was shown to be involved in the H 2 O 2 and • NO systemic signaling as evidenced by real-time labeling of the two molecules. Comparative proteomic analysis identified a number of proteins whose accumulation levels were altered by treatments. They were mainly involved in photosynthesis, defense and energy. More than half of them were commonly modulated by both treatments, indicating a strong overlap between H 2 O 2 and • NO responses. Using a redox proteomic approach, several proteins were also identified as being carbonylation targets of H 2 O 2 and SNP. The analysis reveals an interlinked H 2 O 2 and • NO proteins network allowing a deeper understanding of oxidative and nitrosative signaling in plants.

A series of new hybrid 2-(diethoxyphosphoryl)-N-(benzylidene)propan-2-amine oxide derivatives with different aromatic substitution (PPNs) were synthesized. These molecules were evaluated for their EPR spin trapping potential on eleven different radicals and NO-donation properties in vitro, cytotoxicity and vasoprotective effect on precontracted rat aortic rings. A subfamily of the new PPNs featured an antioxidant moiety occurring in natural phenolic acids. From the experimental screening of these hydroxyphenyl- and methoxyphenyl-substituted PPNs, biocompatible nitrones 4d, and 4g-4i deriving from caffeic, gallic, ferulic and sinapic acids, which combined improved EPR probing of ROS formation, vasorelaxant action and antioxidant potency, might be potential drug candidate alternatives to PBN and its analogues.

AimsOxidation of proteins is presumed to contribute to contractile dysfunction associated with partial outlet obstruction (PBOO) of the urinary bladder. The objective of this study was to determine the acute and chronic effects of PBOO on protein oxidation in urinary bladder detrusor smooth muscle (DSM) and mucosa, and to correlate these findings with in vitro contractile function.MethodsUrinary bladders of New Zealand White (NZW) rabbits were obstructed for 1, 3, 7 and 14 days. Proteins were extracted from the bladder tissues and protein carbonyl formation was assessed using immunoblot assays. In vitro contractile response to field stimulation (32 Hz) and carbachol was evaluated in whole bladder strips at the same time points.ResultsSignificant elevations in oxidation of DSM proteins were observed in the MW range of 29–65 kDa after 3 days and 14 days of obstruction. No changes in the oxidative status of mucosal proteins were detected as a result of short or long term obstruction. T...

Glycolaldehyde (GA) is a highly reactive aldehyde that can be generated during inflammation and hyperglycemia. It can react with arginine and lysine residues impairing protein function. As inflammation and diabetes present haemostatic dysfunction, we hypothesized that GA could participate in this process. The aim of this study was to investigate if plasma incubated in the presence of GA presents alteration in the coagulation process. We also aimed to evaluate the role of fibrinogen in GA-induced haemostatic dysfunction. For this purpose, plasma and fibrinogen were each incubated separately, either in the presence or absence of 1 mM GA for 8 and 4 h, respectively. After that, plasma coagulation and fibrin polymerization kinetics were recorded, as well as the kinetic of plasma clot digestion and fibrinolysis protein carbonylation was quantified. An SDS-PAGE was run to check the presence of cross-linking between fibrinogen chains. GA induced a delay in plasma coagulation and in fibrin polymerization. Maximum absorbance decreased after GA treatment, indicating the generation of thinner fibers. Fibrin generated after complete coagulation showed resistance to enzymatic digestion, which could be related to the generation of thinner fibers. Protein carbonylation also increased after GA treatment. All parameters could be reversed with AMG (a carbonyl trap) co-treatment. The data presented herein indicate that GA causes post-translational modification of lysine and arginine residues, which are central to many events involving fibrinogen to fibrin conversion, as well as to fibrinolysis. These modifications lead to the generation of persistent clots and may contribute to mortality seen in pathologies such diabetes and sepsis.

Background: Increased oxidative/nitrosative stress is important in the pathogenesis of diabetic complications, and the protective effects of antioxidants are a topic of intense research. The purpose of this study was to investigate whether a pyridoindole antioxidant stobadine (STB) have a protective effect on tissue oxidative protein damage represented by the parameters such as protein carbonylation (PC), protein thiol (P-SH), total thiol (T-SH) and non-protein thiol (Np-SH), nitrotyrosine (3-NT), and advanced oxidation protein products (AOPP) in streptozotocin-diabetic rats. Methods: Diabetes was induced in male Wistar rats by intraperitonal injection of streptozotocin (55 mg/kg). Some of the non-diabetic (control) and diabetic rats treated with STB (24.7 mg/kg/day) during 16 weeks, and the effects on blood glucose, PC, AOPP, 3-NT, P-SH, T-SH and Np-SH were studied. Biomarkers were assayed by enzyme-linked immunosorbent assay (ELISA) or by colorimetric methods. Results: Administration of stobadine to diabetic animals lowered elevated blood glucose levels by ∼ 16% relative to untreated diabetic rats. Although stobadine decreased blood glucose, poor glycemic control was maintained in stobadine treated diabetic rats during the treatment period. Biochemical analyses of liver proteins showed significant diminution of sulfhydryl groups, P-SH, T-SH, Np-SH, and elevation of carbonyl groups in diabetic animals in comparison to healthy controls. As a biomarker of nitrosative stress, 3-NT levels did not significantly change by diabetes induction or by stobadine treatment when compared to control animals. However, the treatment with stobadine resulted in a significant decrease in PC, AOPP levels and normalized P-SH, T-SH, Np-SH groups in liver of diabetic animals.

This study investigated the effect of astaxanthin (ASX; 3,3-dihydroxybeta, beta-carotene-4,4-dione), a water-dispersible synthetic carotenoid, on liver ischemia-reperfusion (IR) injury. Astaxanthin (5 mg/kg/day) or olive oil was administered to rats via intragastric intubation for 14 consecutive days before the induction of hepatic IR. On the 15th day, blood vessels supplying the median and left lateral hepatic lobes were occluded with an arterial clamp for 60 min, followed by 60 min reperfusion. At the end of the experimental period, blood samples were obtained from the right ventricule to determine plasma alanine aminotransferase (ALT) and xanthine oxidase (XO) activities and animals were sacrificed to obtain samples of nonischemic and postischemic liver tissue. The effects of ASX on IR injury were evaluated by assessing hepatic ultrastructure via transmission electron microscopy and by histopathological scoring. Hepatic conversion of xanthine dehygrogenase (XDH) to XO, total GSH and protein carbonyl levels were also measured as markers of oxidative stress. Expression of NOS2 was determined by immunohistochemistry and Western blot analysis while nitrate/nitrite levels were measured via spectral analysis. Total histopathological scoring of cellular damage was significantly decreased in hepatic IR injury following ASX treatment. Electron microscopy of postischemic tissue demonstrated parenchymal cell damage, swelling of mitochondria, disarrangement of rough endoplasmatic reticulum which was also partially reduced by ASX treatment. Astaxanthine treatment significantly decreased hepatic conversion of XDH to XO and tissue protein carbonyl levels following IR injury. The current results suggest that the mechanisms of action by which ASX reduces IR damage may include antioxidant protection against oxidative injury.

There is evidence for the role of oxidative stress in severe dengue pathogenesis. However, previous observational studies presents certain methodological limitations, which may affect its internal and external validity. This study was a case-control analysis of patients with severe dengue and dengue with warning signs, to evaluate the serum protein carbonyls-PCOs and lipid hydroperoxides-LOOHs levels and activities of superoxide dismutases-SODs (MnSOD, Cu/ZnSOD and total SOD), as potential prognosis indicators of severity in dengue patients, using binary logistic regression analysis and strategy of double cross-validation. Therefore, the study population was subdivided into a derivation group (pediatric patients, Barranquilla-Colombia) and an external validation group (children and adults patients, National Institute of Health of Peru). PCOs was the only oxidative stress markers that showed a strongest association with the severity of dengue, both in children and adults. In the deri...

Aims: Melanoma is the most aggressive type of malignant skin cancer derived from uncontrolled proliferation of melanocytes. Melanoma cells possess a high potential to metastasize, and the prognosis for advanced melanoma is rather poor due to its strong resistance to conventional chemotherapeutics. Nanomaterials are at the cutting edge of the rapidly developing area of nanomedicine. The potential of nanoparticles for use as carrier in cancer drug delivery is infinite with novel applications constantly being tested. The noncarrier use of cerium oxide nanoparticles (CNPs) is a novel and promising approach, as those particles per se show an anticancer activity via their oxygen vacancy-mediated chemical reactivity. Results: In this study, the question was addressed of whether the use of CNPs might be a valuable tool to counteract the invasive capacity and metastasis of melanoma cells in the future. Therefore, the effect of those nanoparticles on human melanoma cells was investigated in vitro and in vivo. Concentrations of polymer-coated CNPs being nontoxic for stromal cells showed a cytotoxic, proapoptotic, and anti-invasive capacity on melanoma cells. In vivo xenograft studies with immunodeficient nude mice showed a decrease of tumor weight and volume after treatment with CNPs. Innovation: In summary, the redox-active CNPs have selective pro-oxidative and antioxidative properties, and this study is the first to show that CNPs prevent tumor growth in vivo. Conclusion: The application of redox-active CNPs may form the basis of new paradigms in the treatment and prevention of cancers. Antioxid. Redox Signal. 19,[765][766][767][768][769][770][771][772][773][774][775][776][777][778]

The aim of this study was to investigate changes in dietary intake, anthropometric parameters and markers of oxidative stress in 40 women who underwent surgery, chemotherapy or radiation therapy for breast cancer. Pretreatment and post-treatment measurements included data collected through a food frequency questionnaire, weight and height to calculate the body mass index (BMI) and oxidative stress markers assessed from blood reduced glutathione (GSH), serum antioxidant capacity (AC), plasma thiobarbituric acid reactive substances (TBARS), serum lipid hydroperoxides (LH) and plasma carbonyls. Differences were compared using paired Student&#39;s t-test or paired Wilcoxon&#39;s test. A significant increase (P &lt; 0.05) in the intake of the food groups: meat and eggs, dairy products, beans, oils and fats, as well as food from the subgroups: red meat, milk and other dairy products rich in fat, fruit rich in vitamin C and vegetable fats was found after treatments. There was a significant...

Pneumococcal meningitis is associated with a significant mortality rate and neurologic sequelae. The animals received either 10 μL of saline or a S. pneumoniae suspension and were randomized into different groups: sham: placebo with dexamethasone 0.7 mg/kg/1 day; placebo with dexamethasone 0.2 mg/kg/7 days; meningitis groups: dexamethasone 0.7 mg/kg/1 day and dexamethasone 0.2 mg/kg/7 days. Ten days after induction we evaluated memory and oxidative stress parameters in hippocampus and cortex. In the step-down inhibitory avoidance task, we observed memory impairment in the meningitis group with dexamethasone 0.2 mg/kg/7 days. The lipid peroxidation was increased in hippocampus in the meningitis groups with dexamethasone and in cortex only in the meningitis group with dexamethasone 0.2 mg/kg/7 days. The protein carbonyl was increased in hippocampus in the meningitis groups with dexamethasone and in cortex in the meningitis groups with and without dexamethasone. There was a decrease in the proteins integrity in hippocampus in all groups receiving treatment with dexamethasone and in cortex in all groups with dexamethasone (0.7 mg/kg/1 day). The mitochondrial superoxide was increased in the hippocampus and cortex in the meningitis group with dexamethasone 0.2 mg/kg/7 days. Our findings demonstrate that dexamethasone reverted cognitive impairment but increased brain oxidative stress in hippocampus and cortex in Wistar rats ten days after pneumococcal meningitis induction.

To analyze the oxidative damage and histopathological alterations caused by ischemia-reperfusion (I/R) injury and ameliorative effects of carvedilol (CVD) in the rat testis. Twenty-one male rats were randomized into 3 groups as follows: Group I (n = 7); control (sham) group, Group II (n = 7); I/R group, in which I/R injury was performed by torsing the left testis 720 ° clockwise for 2 hours and detorsing for 2 hours. Group III (n = 7); CVD treatment group; in addition to I/R process, one-dose of CVD was administered (2mg/kg, i.p) 30 min. before detorsion. Levels of antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and levels of malondialdehyde (MDA) and protein carbonyl (PC) were determined in testicular tissues and serum of rats. Testicular tissues were also examined histopathologically and Johnsen scores were determined. Activities of SOD and GSH-Px in serum and testicular tissues were increased by I/R, but administration of CVD decreased these le...

1-Methylnicotinamide (MNA), a major endogenous metabolite of nicotinamide, possesses anti-thrombotic and anti-inflammatory activity, and reverses endothelial dysfunction. In the present work, we investigated whether such a vasoprotective profile of MNA activity affords anti-diabetic action in rats. Diabetes was induced by streptozotocin (STZ) in Sprague-Dawley rats. Eight weeks after STZ injection in untreated or MNAtreated rats (100 mg kg -1 daily), development of diabetes (plasma concentrations of fasting and non-fasting glucose, HbA 1c , peptide C), development of oxidant stress (lipid peroxidation, carbonylation of plasma proteins), as well as NO-dependent endothelial function in aorta, coronary and mesenteric vessels were analyzed. Finally, the effect of chronic treatment with MNA on long-term survival of diabetic rats was determined. Chronic treatment with MNA profoundly lowered fasting glucose concentrations in plasma, displayed mild effects on plasma HbA 1c and peptide C concentrations, while having no effects on non-fasting glucose. On the other hand, MNA treatment considerably lowered lipid peroxidation, protein carbonylation, completely prevented impairment of endothelium-dependent vasodilatation in the aorta that was mediated entirely by NO, but failed to affect endothelial function in resistant vessels, which was mediated only partially by NO. Most importantly, chronic treatment with MNA prolonged the long-term survival of diabetic rats. In conclusion, MNA displayed a significant anti-diabetic effect that may be linked to its vasoprotective activity.

Oxidative stress is known by excess production of reactive species, especially (ROS) and deleterious modifications in biomolecules such as proteins, and lipid mainly. It is a common mediator in pathogenesis of multiple diseases. Because of its potential to act as center in the cause of many diseases particularly cardiovascular disease, identifying biomarkers of oxidative stress has become the highly interesting and focus of many research. Measurement of reactive species (ROS) in the circulation of complex biological systems remains a challenge due to the short half-life of these reactive species and the need of special equipment to detect it. A widely used and reliable approach is the measurement of stable by-products modified under conditions of oxidative stress that have entered the circulation. The stable oxidation product that used as biomarker of oxidative stress include lipid oxidation product such as Isoprostanes (isops), MDA, and protein oxidation product such as nitrotyrosine ,Protein Glutathionilation and oxd LDL are the major one. The oxidative stress play pivotal role in the pathogenesis of the major cardiovascular risk factors termed as atherosclerosis. This is caused by excess production of reactive species (ROS) in the vessel mainly by enzymes such as NAD (P)H oxidase, xanthine oxidase, myeloperoxidase and uncoupled nitrc oxide synthase which oxidize lipoprotein (LDL). The oxidize LDL (oxLDL) lipoprotein progress the atherosclerosis process from the initially to the end stage development.

The development of cognitive impairment in sepsis is associated with neurotoxic effects caused by oxidative stress. We have assessed the effects of acute and extended administration of guanosine (GUA) on brain oxidative stress parameters and cognitive impairment in rats submitted to sepsis by cecal ligation and perforation (CLP). To achieve this goal, male Wistar rats underwent either sham operation or CLP with GUA. Rats subjected to CLP were treated with intraperitoneal injection of GUA (8 mg/kg after CLP) or vehicle. Twelve and 24 h after CLP, the rats were sacrificed, and samples from brain (hippocampus, striatum, cerebellum, prefrontal cortex and cortex) were obtained and assayed for thiobarbituric acid reactive species (TBARS) formation and protein carbonyls. On the 10th day, another group of rats was submitted to the behavioral tasks. GUA administration reduced TBARS and carbonyl levels in some brain regions between 12 and 24 h after CLP, and ameliorated cognitive impairment evaluated 10 days after CLP. Our data provide the first experimental demonstration that GUA was able to reduce the consequences of CLP-induced sepsis in rats, by decreasing oxidative stress parameters in the brain and recovering the memory impairment.

The present study aimed to evaluate cardio-protective effect of Nigella sativa oil (NSO) on lead induced cardio toxicity. Forty five albino adult rats were randomly divided into 3 groups: control lead (Pb) group that received lead acetate (20 mg/kg/day) 3 times weekly for 8 weeks and PB + NSO group (rats pretreated with Nigella sativa oil (4 ml/kg) orally for 1 h before administration of lead acetate (given as in Pb group). Myocardial injury was assessed by laboratory and pathological studies, and heart rate was recorded in all animals. Lead intake resulted in significant increases in cardiac high-sensitivity Creactive protein (hs-CRP), interlukin-6 (IL-6), E-selectin, troponin I, malondialdehyde (MDA) and serum creatine kinase-MB (CK-MB). The cardiac apelin, superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH) levels significantly decreased in Pb group compared to the control. Currently, heart rate and ST segment increased significantly after lead intake. Heart lesions as a result of lead treatment were in the form of hemorrhage, myocardial necrosis, mononuclear cell infiltration and fibrosis. Immuno histochemical results of the heart revealed positive cyclooxyenase-2 (Cox-2) expressions in Pb-treated group. NSO administration produced significant normalization of the physiological parameters as well as restored the histological structure and decreased the COX-2 expression of the heart compared to Pb group. In conclusion, NSO intake has cardio protective potential through its ability to decrease pro inflammatory cytokines, oxidative stress and cardiac tissue damage in lead-induced cardio toxicity.

A number of C-3 spirocyclic 2-benzazepine analogs of a-phenyl-N-tert-butyl nitrone (PBN) were synthesized and tested for their activity in protecting rat brain mitochondria and dopaminergic (DA) neurons against 6-hydroxydopamine (6-OHDA), a toxin inducing destruction of the DA nigrostriatal pathway in rodent models of Parkinson's disease. The newly synthesized nitrone derivatives were firstly investigated for their activity in decreasing the level of hydroxyl radicals generated during 6-OHDA oxidation, and inhibit lipid peroxidation (TBARS assay) and protein carbonyl content (PCC) in rat brain mitochondria. Most of the studied 2-benzazepine nitrones showed inhibitory potencies in both TBARS and PCC assays at least two magnitude orders higher than that of PBN. The data obtained usefully complemented the known structure-activity relationships. In particular, 5 and 10, bearing C-3 spiro cyclopentyl and tetrahydropyranyl moieties, respectively, at 8 mM concentration proved to be significantly more effective than PBN in protecting cultured DA neurons exposed to 6-OHDA, which alone causes about 45% cell loss in 24 h. In addition, we found that 5 inhibited butyrylcholinesterase with an IC 50 value of 16.8 mM, which would enhance its potential as neuroprotective agent in Alzheimer's neurodegeneration. These findings extend the utility of benzazepine-based PBN analogs in the treatment of age-related free radical-mediated disorders.

Saccharomyces cerevisiae was used to uncover the mechanisms underlying tolerance and toxicity of the agricultural fungicide mancozeb, linked to cancer and Parkinson's disease development. Chemogenomics screening of a yeast deletion mutant collection revealed 286 genes that provide protection against mancozeb toxicity. The most significant Gene Ontology (GO) terms enriched in this dataset are associated to transcriptional machinery, vacuolar organization and biogenesis, intracellular trafficking, and cellular pH regulation. Clustering based on physical and genetic interactions further highlighted the role of oxidative stress response, protein degradation and carbohydrate=energy metabolism in mancozeb stress tolerance. Mancozeb was found to act in yeast as a thiolreactive compound, but not as a free radical or reative oxygen species (ROS) inducer, leading to massive oxidation of protein cysteins, consistent with the requirement of genes involved in glutathione biosynthesis and reduction and in protein degradation to provide mancozeb resistance. The identification of Botrytis cinerea homologues of yeast mancozeb tolerance determinants is expected to guide studies on mancozeb mechanisms of action and tolerance in phytopathogenic fungi. The generated networks of protein-protein associations of yeast mancozeb tolerance determinants and their human orthologues share a high degree of similarity. This toxicogenomics analysis may, thus, increase the understanding of mancozeb toxicity and adaptation mechanisms in humans.

Alkaptonuria (AKU) is a rare genetic disease associated with the accumulation of homogentisic acid (HGA) and its oxidized/polymerized products in connective tissues up to the deposition of melanin-like pigments (ochronosis). Since little is known on the effects of HGA and its metabolites on articular cells, we carried out a proteomic and redox-proteomic analysis to investigate how HGA and ascorbic acid (ASC) affect the human chondrocytic protein repertoire. We settled up an in vitro model using a human chondrocytic cell line to evaluate the effects of 0.33 mM HGA, alone or combined with ASC. We found that HGA and ASC significantly affect the levels of proteins with specific functions in protein folding, cell organization and, notably, stress response and cell defense. Increased protein carbonyls levels were found either in HGA or ASC treated cells, and evidences produced in this paper support the hypothesis that HGA-induced stress might be mediated by protein oxidation. Our finding can lay the basis towards the settling up of more sophisticated models to study AKU and ochronosis.

Interaction between antigen presenting cells and T lymphocytes, through receptors and co-stimulatory molecules present on the surface of these cells, is one of the key means to modulate the adaptive immune system. Tucaresol, a Schiff-base-forming chemical, can be used as a substitute for the physiological donor of carbonyl groups of antigen presenting cells, which can interact with the amine groups of T lymphocytes to modulate the adaptive immune system. This study was done to determine whether tucaresol can enhance killing of cancer cells in vitro as well as protect non-obese diabetic severe combined immunodeficient mice from tumor development by mucin 1 stimulated human mononuclear cells through the adaptive immune system. The expected hypothesis was not supported. Percent specific lysis of MCF-7 tumor cells by mucin 1 stimulated human mononuclear cells was reduced by tucaresol. Furthermore, tucaresol abolished the protective effect of mucin 1 stimulated human mononuclear cells against MCF-7 breast cancer cell growth in non-obese diabetic severe combined immunodeficient mice. This study implies that tucaresol may be of use as an immunosuppressive agent.

To clarify the effects of selenium, parameters related to oxidative issues, as well as the antioxidant response were investigated on an autochthonous wine yeast strain. Antioxidant enzyme activity, Gel electrophoresis, Western Blot and MDA level were used to investigate the effects of different concentration of selenium in wine yeast. We found that selenium is able to affect the enzymatic activities of catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase (SOD). An increase of lipid peroxidation was observed in a dose dependent manner of (Se), thus, indicating the occurrence of cell membrane damage. Additionally, Selenium induced post-translational oxidative modifications of proteins, especially oxidation of thiol groups (both reversible and irreversible) and protein carbonylation (irreversible oxidation). These results obtained could further the understanding the effect of different concentration of selenium in wine yeast strain with which Selenium affect the enzymatic activities and induces some Post-translational Modifications of Proteins. The understanding of mechanisms regulating the response of wine yeast to selenium is important for future work using of selenized yeast as enriched selenium supplements in human nutrition.

LCA and 1,25(OH)2D3 are vitamin D receptor ligands with different binding affinity. The secosteroid stimulates intestinal Ca(2+) absorption. Whether LCA alters this process remains unknown. The aim of our work was to determine the effect of LCA on intestinal Ca(2+) absorption in the absence or presence of NaDOC, bile acid that inhibits the cation transport. The data show that LCA by itself did not alter intestinal Ca(2+) absorption, but prevented the inhibitory effect of NaDOC. The concomitant administration of LCA avoided the reduction of intestinal alkaline phosphatase activity caused by NaDOC. In addition, LCA blocked a decrease caused by NaDOC on gene and protein expression of molecules involved in the transcellular pathway of intestinal Ca(2+) absorption. The oxidative stress and apoptosis triggered by NaDOC were abrogated by LCA co-treatment. In conclusion, LCA placed in the intestinal lumen protects intestinal Ca(2+) absorption against the inhibitory effects caused by NaDOC. ...

The aim of this study was to establish the protective effect of caffeic acid phenethyl ester (CAPE) against the ifosfamide (IFOS)-induced central neurotoxicity in rats and to determine the changes in oxidant-antioxidant status of brain tissue. Method: A total of 35 Wistar rats (aged 7-12 days) were used in the experiments. The study comprised of five groups. Control untreated rats (n = 7) belonged to group 1; group 2 was given intraperitoneal (IP) injection of CAPE alone (10 µmol/kg; n = 7); group 3 was treated with single IP injection of IFOS (500 mg/kg; n = 7); group 4 was treated for 2 days with IP administration of CAPE (10 µmol/kg) beginning from one day before single IP injection of IFOS (n = 7); and group 5 was treated with saline and 10% ethanol. At the 24th hour of IFOS treatment, brain tissues were removed for analysis. The brain catalase activity was lower in IFOS group than the other groups (p &lt; 0.05). The levels of malondialdehyde (MDA) and protein carbonyl content i...

Aim: This study investigated the protective effects of sildenafil (SIL) and resveratrol (RSV) on ovarian ischemia-reperfusion (I/R) injury. Materials and methods: Forty-Eight Wistar albino rats were divided equally into groups: control (sham), ischemia (2 h ischemia), I/R (2 h ischemia+2 h reperfusion), I/R+RSV (10 mg/kg intraperitoneally), I/R+SIL (1.4 mg/kg intraperitoneally), and I/R+RSV+SIL. RSV and SIL were administered 30 min before the end of the ischemia period, and reperfusion was carried out for 2 h. The ovaries were then removed and evaluated histopathologically for mean histopathological damage score (MHDS) and anti-inducible nitric oxide (NO) synthase (iNOS) antibody. Malondialdehyde (MDA) level, glutathione (GSH) activity, total antioxidant status (TAS), total oxidant status (TOS), and NO level were measured. Results: Histopathological findings such as enema, inflammation, haemorrhage, and congestion were detected in the ischemia and I/R groups. Compared with controls, these groups had significantly higher MHDSs. Compared with the ischemia and I/R groups, the treatment groups had significantly decreased MHDSs. iNOS immunostaining was most evident in the ischemia and I/R groups, and TOS and MDA and NO levels were significantly increased, whereas GSH activity and TAS were significantly decreased compared with those in controls. TOS and MDA and NO levels were significantly decreased, and GSH activity and TAS were significantly increased in the treatment groups. Conclusion: RSV and SIL decreased histopathological and biochemical damage and exerted protective effects on I/R-induced ovarian damage. SIL and RSV act simultaneously to reduce tissue injury.

The healing activity of the methanol extract of the spice rampatri, Myristica malabarica, (RM) and omeprazole against indometacin-induced stomach ulceration has been studied in a mouse model. Treatment with RM (40 mg kg−1 per day) and omeprazole (3 mg kg−1 per day) for 3 days could effectively heal the stomach ulceration, as revealed from the ulcer indices and histopathological studies. Compared with the ulcerated group, treatment with RM and omeprazole for 3 days reduced the macroscopic damage score by approximately 72% and 76%, respectively (P &lt; 0.001), establishing the efficacy of RM. The extent of ulcer healing offered by 3 days&#39; treatment with RM or omeprazole was better than that observed with natural recovery over 5 and 7 days (P &lt; 0.05). The healing capacities of RM and omeprazole could be attributed to their antioxidant activity as well as the ability to enhance the mucin content of the gastric tissues. Both drugs reduced lipid peroxidation (by 42–44%) and protein...

Differential proteomics is considered as one of the most powerful tools for evaluating relative expression of molecular moieties either in plants or animals. The present study focuses first on optimizing a rapid and sensitive protocol for the isolation of high quality protein to be used in two dimensional gel electrophoresis (2DE) from date palm samples, and then comparing differentially expressed peptides associated with red palm weevil (RPW) infestation of this plant using uninfested plants as control. Among the several methodologies we used for optimization, it was revealed that Phenol/ SDS extraction followed by methanolic ammonium acetate precipitation (designated as protocol 3 in this study) yielded high quality protein. Moreover, 2DE protein analysis demonstrated both qualitative and quantitative differences between control and infested date palm samples. Our differential proteomic methodologies showed 22 differential spots having modulation level ≥1.5 fold. Subsequently, these differentially expressed peptides were subjected to MALDI-TOF peptide mass fingerprinting analysis for their characterization. The 11 peptides identified through these methodologies fall into three major functional groups including stress/defense (5), photosynthesis (2), ion transport (1) related proteins and three with other functions. Our data revealed that proteins related to date palm defense or stress response were up-regulated in infested samples while the proteins involved in photosynthetic activities were down regulated. The present results indicated that RPW infestation of date palm plants induced molecular changes manifested through differential expression of proteins. Differentially expressed peptides besides increasing our understanding relevant to RPW infestation will help us in developing methodologies for early detection of RPW infestation beneficial for curbing this problem in economically important date palm trees.

The cnidarian-dinoflagellate symbiosis is a mutualistic intracellular association based on the photosynthetic activity of the endosymbiont. This relationship involves significant constraints and requires co-evolution processes, such as an extensive capacity of the holobiont to counteract pro-oxidative conditions induced by hyperoxia generated during photosynthesis. In this study, we analyzed the capacity of Anemonia viridis cells to deal with pro-oxidative conditions by in vivo and in vitro approaches. Whole specimens and animal primary cell cultures were submitted to 200 and 500 μM of H2O2 during 7 days. Then, we monitored global health parameters (symbiotic state, viability, and cell growth) and stress biomarkers (global antioxidant capacity, oxidative protein damages, and protein ubiquitination). In animal primary cell cultures, the intracellular reactive oxygen species (ROS) levels were also evaluated under H2O2 treatments. At the whole organism scale, both H2O2 concentrations d...

Cystinosis is a systemic genetic disease caused by a lysosomal transport deficiency accumulating cystine in most tissues. Tissue damage depends on cystine accumulation, but the mechanisms of this damage are still obscure. Cysteamine administration depletes cystine accumulated, increasing survive of affected patients. Studies performed in fibroblasts of cystinotic patients suggest that apoptosis is enhanced in this disease. Considering that oxidative stress is a known apoptosis inducer, our main objective was to investigate a possible antioxidant effect of cysteamine on several parameters of oxidative stress in the brain of young rats. Animals received three subcutaneous injections at 3-h intervals of a buffered solution (pH 7.4) of 10 mg/kg body weight cysteamine and were sacrificed 1 h after the last injection. Cysteamine decreased lipoperoxidation and glutathione peroxidase activity, and increased the carbonyl content of proteins and catalase activity. In vitro studies