Colon cancer is the third most common malignant neoplasm in the world and it remains an important... more Colon cancer is the third most common malignant neoplasm in the world and it remains an important cause of death, especially in western countries. The toxic environmental pollutant, 1, 2-dimethylhydrazine (DMH), is also a colon-specific carcinogen. Tannic acid (TA) is reported to be effective against various types of chemically induced toxicity and also carcinogenesis. In the present study, we evaluated the chemopreventive efficacy of TA against DMH induced colon toxicity in a rat model. Efficacy of TA against the colon toxicity was evaluated in terms of biochemical estimation of antioxidant enzyme activities, lipid peroxidation, histopathological changes and expression of early molecular markers of inflammation and tumor promotion. DMH treatment induced oxidative stress enzymes (p<0.001) and an early inflammatory and tumor promotion response in the colons of Wistar rats. TA treatment prevented deteriorative effects induced by DMH through a protective mechanism that involved reduction of oxidative stress as well as COX-2, i-NOS, PCNA protein expression levels and TNF-α (p<0.001) release. It could be concluded from our results that TA markedly protects against chemically induced colon toxicity and acts plausibly by virtue of its antioxidant, anti-inflammatory and antiproliferative activities.
Trichloroethylene-mediated cytotoxicity in human epidermal keratinocytes is mediated by the rapid accumulation of intracellular calcium: Interception by naringenin
Human & experimental toxicology, Jan 8, 2015
Industrial solvents pose a significant threat to the humankind. The mechanisms of their toxicity ... more Industrial solvents pose a significant threat to the humankind. The mechanisms of their toxicity still remain in debate. Trichloroethylene (TCE) is a widespread industrial solvent responsible for severe liver dysfunction, cutaneous toxicity in occupationally exposed humans. We utilized an in vitro system of human epidermal keratinocyte (HaCaT) cells in this study to avoid complex cell and extracellular interactions. We report the cytotoxicity of organic solvent TCE in HaCaT and its reversal by a natural flavanone, naringenin (Nar). The cytotoxicity was attributed to the rapid intracellular free calcium (Ca(2+)) release, which might lead to the elevation of protein kinase C along with robust free radical generation, instability due to energy depletion, and sensitization of intracellular stress signal transducer nuclear factor κB. These effects were actually seen to induce significant amount of genomic DNA fragmentation. Furthermore, all these effects of TCE were effectively reversed ...
Suppression of inflammatory response by chrysin, a flavone isolated from Potentilla evestita Th. Wolf. In silico predictive study on its mechanistic effect
Fitoterapia, 2015
Flavonoids are the most abundant natural polyphenols widely distributed in plants. Among them, ch... more Flavonoids are the most abundant natural polyphenols widely distributed in plants. Among them, chrysin has recently attracted the attention for its anti-tumor and anti-oxidant activities and also for its protective effects on allergic inflammation. Therefore, in this study, we set out to investigate and characterize the effects of chrysin in classical models of inflammation reasoning that this would expand our knowledge on the pharmacological properties of this flavone. To this aim we have firstly isolated chrysin from Potentilla evestita Th. Wolf. and successively evaluated its anti-inflammatory and analgesic potential on writhing and formalin test and also on carrageenan-induced paw oedema. Finally, the present study was planned to investigate, by the aim of docking analysis, the molecular interaction of this compound on the binding site of COX-1 and COX-2 enzymes. On writhing test, we observed a significant inhibition of writhings after the administration of chrysin at 5.0 and 10.0mg/kgi.p. (25.00±9.22% and 55.67±7.62% respectively). On formalin test, the flavone at dose of 10.0mg/kgi.p. displayed its maximum analgesic and anti-inflammatory effect on both early (35.67±7.88%) and late phase (50.57±5.36%) and similarly displayed at 4h a significant anti-inflammatory effect in carrageenan-induced paw oedema. Moreover, in silico analysis of receptor ligand complex shows that chrysin interacts weakly with COX-1 binding site whereas displayed a remarkable interaction with COX-2. These findings suggest that the flavone chrysin isolated from P. evestita Th. Wolf. possesses in vivo anti-inflammatory and anti-nociceptive potential, which are supported in silico by an interaction with COX-2 binding site.
MP75-13 Stone Culture for Patients Undergoing Flexible Ureteroscopy (Furs) and Laser Stone Fragmentation for Renal Stone – Does It Add Anything to Management?
To investigate the bone regenerative effect of polymer and collagen incorporation to synthetic bo... more To investigate the bone regenerative effect of polymer and collagen incorporation to synthetic bone graft materials. The bone ingrowth of biphasic graft materials was tested in a rabbit calvaria defect model after chemical characterization: HA/TCP (25%/75%) with collagen, HA/TCP (25%/75%) without collagen, (HA/TCP)/PLGA (85%/15%) with collagen, (HA/TCP)/PLGA (65%/35%) with collagen and a commercially available (HA/TCP)/PLGA (50%/50%) was used as control. After 4 and 8 weeks, the retrieved samples were subjected to histomorphometrical analysis. Histomorphometry presented no significant differences concerning the bone formation between the different groups at both 4 and 8 weeks. Evidently, the (HA/TCP)/PLGA (65%/35%) with collagen presented the least amount of soft tissue incorporation within the defect. The same group possessed higher amounts of bone graft material within the defect throughout the 8-week observation period, whereas the other groups seemed to decrease in volume from 4...
Purpose To evaluate ocular surface of chronic graft versus host disease (GVHD) patients in alloge... more Purpose To evaluate ocular surface of chronic graft versus host disease (GVHD) patients in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods Cross-sectional study of allo-HSCT patients. Data recorded included Ocular Surface Disease Index (OSDI) score, fluorescein tear break-up time (FTBUT), Schirmer I test, ocular surface staining, dry eye severity, and conjunctival impression cytology (CIC). Results Of 40 allo-HSCT patients (mean age 25.7 ± 11.03 years) studied, dry eye disease was noted in 30%. The OSDI was mild in 16.67%, moderate in 45.83%, and severe in 20.83% ocular GVHD (oGVHD) eyes; mild in 94.64%, moderate in 5.36% non-oGVHD eyes (p<0.001). The FTBUT was ≤5 seconds in 45.83%, >5 seconds in 54.17% of eyes with chronic oGVHD. Schirmer I test score was ≤5 mm in 58.33% of eyes with oGVHD. Conjunctival staining score was <3 in 25%, ≥3 in 75% of oGVHD eyes. Corneal staining score of <3 in 79.17%, ≥3 in 20.83% was seen in oGVHD eyes. Chronic oGVHD...
The major constraint on the performance of orthogonal frequency division multiplexing (OFDM) base... more The major constraint on the performance of orthogonal frequency division multiplexing (OFDM) based underwater acoustic (UWA) communication is to keep subcarriers orthogonal. In this paper, Doppler estimation and the respective compensation technique along with various diversity techniques were deliberated for OFDM-based systems best suited for underwater wireless information exchange. In practice, for mobile communication, adjustment and tuning of transducers in order to get spatial diversity is extremely difficult. Considering the relatively low coherence bandwidth in UWA, the frequency diversity design with the Doppler compensation function was elaborated here. The outfield experiments of mobile underwater acoustic communication (UWAC) based on OFDM were carried out with 0.17 bit/(s•Hz) spectral efficiency. The validity and the dependability of the scheme were also analyzed.
Clinica chimica acta; international journal of clinical chemistry, Jan 23, 2015
Multiple myeloma (MM) represents a malignancy of B-cells characterized by proliferation of malign... more Multiple myeloma (MM) represents a malignancy of B-cells characterized by proliferation of malignant plasma cells in the bone marrow (BM). Versican (VCAN), an extracellular matrix (ECM) protein, appears to be involved in multiple processes in several cancers. Identifying optimum diagnostic markers and delineating its association with disease severity might be important for controlling MM. Expression of VCAN and its associated molecules (β-catenin, β1-integrin and FAK) were investigated in 60 subjects to evaluate their usefulness as diagnostic marker. Circulatory and molecular levels of above molecules were analyzed in their BM and Blood using ELISA, Q-PCR and western blotting along with their ROC curve analysis. Circulatory levels of VCAN, β-catenin and FAK were significantly higher in patients with varying significance in each stage. β-Catenin and FAK intracellular levels were significantly elevated in patients. mRNA levels of all molecules were significantly higher in BMMNCs while...
Kinetic Study of Containment Retention Factor (CRF) for Large Dry Containment Under Radiation Load
Volume 3: Next Generation Reactors and Advanced Reactors; Nuclear Safety and Security, 2014
The Nuclear Power Plants (NPPs) have been built on the concept of Defense in depth. The severe ac... more The Nuclear Power Plants (NPPs) have been built on the concept of Defense in depth. The severe accident causes the failure of fission product barriers and let the fission products to escape into environment. The containment is the last barrier to the fission products. Thus, the containment is installed with engineering safety features (ESFs) i.e. spray system, heat removal system, recirculation filtration system; containment filtered venting system (CFVS), and containment exhaust filtration system. In this work, kinetic study of the containment retention factor (CRF) has been carried out for a large dry PWR containment considering 1000 MWe PWR. The computational modeling and simulation have been carried out by developing a kinetic code in MATLAB, which uses the fractions of activity airborne into the containment after the accident. The Kinetic dependency of CRF on containment filtration systems, spray system with caustic and boric acid spray has been carried out. For noble gases, io...
Skin cancer is the most common malignancy in the world and also one of the major causes of death ... more Skin cancer is the most common malignancy in the world and also one of the major causes of death worldwide. The toxic environmental pollutant 7,12dimethylbenz[a]anthracene (DMBA) is a skin-specific carcinogen. Tannic acid (TA) is reported to be effective against various types of chemical-induced toxicities and carcinogenesis as well. In the present study, we have evaluated the therapeutic potential of tannic acid in DMBA ? croton oilinduced skin cancer in Swiss albino mice. Protective effect of TA against skin cancer was evaluated in terms of antioxidant enzymes activities, lipid peroxidation, histopathological changes and expression of inflammation and early tumour markers. DMBA ? croton oil causes depletion of antioxidant enzymes (p \ 0.001) and elevation of early inflammatory and tumour promotional events. TA prevents the DMBA ? croton oil-induced toxicity through a protective mechanism that involves the reduction of oxidative stress as well as COX-2, i-NOS, PCNA protein expression and level of proinflammatory cytokine such as IL-6 release at a very significant level (p \ 0.001). It could be concluded from our results that TA attenuates DMBA ? croton oil-induced tumour promotional potential possibly by inhibiting oxidative and inflammatory responses and acts as antioxidant, anti-inflammatory and antiproliferative agent.
Chrysin protects against cisplatin-induced colon. toxicity via amelioration of oxidative stress and apoptosis: Probable role of p38MAPK and p53
Toxicology and Applied Pharmacology, 2012
Cisplatin, an antineoplastic drug, is widely used as a foremost therapy against numerous forms of... more Cisplatin, an antineoplastic drug, is widely used as a foremost therapy against numerous forms of cancer but it has pronounced adverse effects viz., nephrotoxicity, ototoxicity etc. CDDP-induced emesis and diarrhea are also marked toxicities that may be due to intestinal injury. Chrysin (5,7-dihydroxyflavone), a natural flavone commonly found in many plants possesses multiple biological activities, such as antioxidant, anti-inflammatory and anti-cancer effects. In the present study, we investigated the protective effect of chrysin against CDDP-induced colon toxicity. The plausible mechanism of CDDP-induced colon toxicity and damage includes oxidative stress, activation of p38MAPK and p53, and colonic epithelial cell apoptosis via upregulating the expression of Bak and cleaved caspase-3. Chrysin was administered to Wistar rats once daily for 14 consecutive days at the doses of 25 and 50 mg/kg body weight orally in corn oil. On day 14, a single intraperitoneal injection of cisplatin was given at the dose of 7.5 mg/kg body weight and animals were euthanized after 24 h of cisplatin injection. Chrysin ameliorated CDDP-induced lipid peroxidation, xanthine oxidase activity, glutathione depletion, decrease in antioxidant (catalase, glutathione reductase, glutathione peroxidase and glucose-6 phosphate dehydrogenase) and phase-II detoxifying (glutathione-S-transferase and quinone reductase) enzyme activities. Chrysin also attenuated goblet cell disintegration, expression of phospho-p38MAPK and p53, and apoptotic tissue damage which were induced by CDDP. Histological findings further supported the protective effects of chrysin against CDDP-induced colonic damage. The results of the present study suggest that the protective effect of chrysin against CDDP-induced colon toxicity was related with attenuation of oxidative stress, activation of p38MAPK and p53, and apoptotic tissue damage.
Central to the concept of attention is the fact that identical stimuli can be processed in differ... more Central to the concept of attention is the fact that identical stimuli can be processed in different ways. In olfaction, attention may designate the identical flow of air through the nose as either respiration or olfactory exploration. Here we have used functional magnetic resonance imaging (fMRI) to probe this attentional mechanism in primary olfactory cortex (POC). We report a dissociation in POC that revealed attention-dependent and attention-independent subregions. Whereas a temporal subregion comprising temporal piriform cortex (PirT) responded equally across conditions, a frontal subregion comprising frontal piriform cortex (PirF) and the olfactory tubercle responded preferentially to attended sniffs as opposed to unattended sniffs. In addition, a task-specific anticipatory response occurred in the attention-dependent region only. This dissociation was consistent across two experimental designs: one focusing on sniffs of clean air, the other focusing on odor-laden sniffs. Our findings highlight the role of attention at the earliest cortical levels of olfactory processing.
The growth and development of prostate gland is governed by testosterone. Testosterone helps in m... more The growth and development of prostate gland is governed by testosterone. Testosterone helps in maintaining the adipose tissue stores of the body. It is well documented that with advancing age there has been a gradual decline in testosterone levels. Our aim was to study the protective role of daidzein on flutamide-induced androgen deprivation on matrix degrading genes, lipid profile and oxidative stress in Wistar rats. Sub-chronic (60 days) flutamide (30 mg/kg b.wt) administration resulted in marked increase in expressions of matrix degrading genes [matrix metalloproteases 9 and urokinase plasminogen activation receptor]. Additionally, it increased the levels of low density lipoproteins, total cholesterol, triglycerides, and lowered the levels of high density lipoproteins and endogenous antioxidant levels. Oral administration of daidzein (20 and 60 mg/ kg b.wt) restituted the levels to normal. Daidzein administration resulted in amelioration of the prostate atrophy, degeneracy and invasiveness induced by flutamide. Our findings suggest that the daidzein may be given as dietary supplement to patients who are on androgen deprivation therapy, to minimize the adverse effects related to it and also retarding susceptibility of patients to cardiovascular diseases. Keywords Androgen receptor (AR) Á Flutamide Á Matrix metalloproteases 9 (MMP-9) Á Daidzein Á Urokinase plasminogen activation receptor (uPAR) Á Cholesterol Abbreviations AR Androgen receptor BPH Benign prostatic hyperplasia CDNB 1-Chloro 2,4-dinitrobenzene CaP Cancer of prostate CAT Catalase CVD's Cardiovascular diseases DTNB 5,5 0-Dithio-bis [2-nitrobenzoic acid]
Structural determination of daphnecin, a new coumarinolignan fromDaphne mucronata
Journal of Asian Natural Products Research, 2010
Daphnecin (1), a new coumarinolignan, has been isolated from the ethyl acetate-soluble fraction o... more Daphnecin (1), a new coumarinolignan, has been isolated from the ethyl acetate-soluble fraction of Daphne mucronata along with three known compounds, aquillochin (2), umbelliferone (3), and coumarin (4). Their structures were determined by spectroscopic studies.
and-conditions-of-access.pdf This article may be used for research, teaching and private study pu... more and-conditions-of-access.pdf This article may be used for research, teaching and private study purposes. Any substantial or systematic reproduction, redistribution , reselling , loan or sub-licensing, systematic supply or distribution in any form to anyone is expressly forbidden. The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material.
Although nonalcoholic steatohepatitis (NASH) is typically associated with obesity, it has also be... more Although nonalcoholic steatohepatitis (NASH) is typically associated with obesity, it has also been reported to occur in lean individuals exposed to industrial chemicals. Occupational exposure to vinyl chloride (VC) is a well-documented risk factor for hemangiosarcoma, but has not previously been associated with steatohepatitis. Here, we evaluate liver biopsies from 25 nonobese, highly-exposed, VC workers for steatohepatitis. Next, we evaluate associated metabolic and cytokine abnormalities in affected workers controlled by 26 chemical workers with no to minimal VC exposures, and 11 unexposed, healthy volunteers. Among highly-exposed VC workers, the prevalence of steatohepatitis was 80%. Of these, 55% had fibrosis and four had hemangiosarcoma. We have coined the term, toxicant-associated steatohepatitis (TASH), to describe this condition which was not explained by obesity or alcohol. Although mean serum transaminases were normal in TASH, total cytokeratin18, but not the caspase-cleaved fragment, was elevated. Despite the absence of obesity, workers with TASH had insulin resistance with reduced adiponectin levels. TASH was also associated with markedly elevated serum tumor necrosis factor alpha and interleukins 1β, 6, and 8. Serum antioxidant activity was reduced in TASH. Conclusion-TASH occurred frequently in these non-obese VC workers with high cumulative exposures and normal liver enzymes. Elevated total cytokeratin 18 suggested the presence of necrotic cell death in TASH and may be a useful serologic biomarker. TASH was further characterized by insulin resistance, elevated pro-inflammatory cytokines, and impaired antioxidant defenses. The threshold VC exposure and the role of other chemical agents in TASH are as yet unknown.
Polyphenols are the abundant micronutrient in our diet and attention has been given to them for t... more Polyphenols are the abundant micronutrient in our diet and attention has been given to them for the prevention of degenerative diseases. Since over production of ROS and proinflammatory cytokine are often act as the triggers for the promotion stage of carcinogenesis by transcriptional up-regulation of nuclear factor-jB (NF-jB) and cycloxygenage-2 (COX-2). We investigated the protective effects of caffeic acid (CA) on 12-O-tetradecanoyl-phorbol-13-acetate (TPA) induced oxidative and inflammatory responses, expression of NF-jB and COX-2 in mouse skin. Animals were given pre-treatment of CA at two different doses 10 lmol (D1) and 20 lmol (D2)/0.2 ml of acetone 30 min prior to each TPA (10 nmol/0.2 ml of acetone) application. Our results show that CA significantly inhibit the TPA induced lipid peroxidation (LPO), inflammatory responses, tumor necrosis factor alpha (TNF-a) release and also found to up regulate GSH content and the activity of different antioxidant enzymes. Further, CA was found to inhibit the TPA induced expression of NF-jB and COX-2. Thus, our results suggest that CA attenuates TPA induced tumor promotional triggers possibly by inhibition of oxidative and inflammatory responses thereby diminishing the expression of NF-jB and COX-2.
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