Heme Biosynthesis

Heme A is a prosthetic group unique for cytochrome a-type respiratory oxidases in mammals, plants and many microorganisms. The poorly understood integral membrane protein heme A synthase catalyzes the synthesis of heme A from heme O. In bacteria, but not in mitochondria, this enzyme contains one or two pairs of cysteine residues that are present in predicted hydrophilic polypeptide loops on the extracytoplasmic side of the membrane. We used heme A synthase from the eubacterium Bacillus subtilis and the hyperthermophilic archeon Aeropyrum pernix to investigate the functional role of these cysteine residues. Results with B. subtilis amino acid substituted proteins indicated the pair of cysteine residues in the loop connecting transmembrane segments I and II as being essential for catalysis but not required for binding of the enzyme substrate, heme O. Experiments with isolated A. pernix and B. subtilis heme A synthase demonstrated that a disulfide bond can form between the cysteine res...

Human porphobilinogen deaminase (PBGD), the third enzyme in the heme pathway, catalyzes four times a single reaction to convert porphobilinogen into hydroxymethylbilane. Remarkably, PBGD employs a single active site during the process, with a distinct yet chemically equivalent bond formed each time. The four intermediate complexes of the enzyme have been biochemically validated and they can be isolated but they have never been structurally characterized other than the apo-and holo-enzyme bound to the cofactor. We present crystal structures for two human PBGD intermediates: PBGD loaded with the cofactor and with the reaction intermediate containing two additional substrate pyrrole rings. These results, combined with SAXS and NMR experiments, allow us to propose a mechanism for the reaction progression that requires less structural rearrangements than previously suggested: the enzyme slides a flexible loop over the growing-product active site cavity. The structures and the mechanism proposed for this essential reaction explain how a set of missense mutations result in acute intermittent porphyria.

Moringa oleifera Lam. (Moringaceae) is a medicinally important plant, used as traditional medicine all over the world particularly in South Asia and India. Hydroalcoholic (50% v/v) root extract of M. oleifera (150 mg/kg, p.o.) with piperine (2.5 mg/kg, p.o), or curcumin (5.0 mg/kg, p.o.) was administered daily for 1 week in Female Wistar albino rats against beryllium toxicity (1.0 mg/kg, i.p. daily for 5 weeks). Beryllium altered hepatorenal function and enhanced the leakage of AST, ALT, and LDH, depleted SALP activity, and increased the level of urea, uric acid, creatinine, triglyceride and total cholesterol in the blood. Beryllium altered tissue biochemical parameters by a decrease in SDH, ALPase, ATPase activities, and increased ACPase activity, depleted hemoglobin and ALAD activity with an increase in ALAS activity and serum bilirubin. A significant amount of beryllium deposited in the liver, kidney, spleen, and bones. M. oleifera with curcumin showed better antitoxic potential ...

Fil: Buzaleh, Ana Maria. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Centro de Invest. Sobre Porfirinas y Porfirias; Argentina. Hospital 12 de Octubre; Espana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Quimica Biologica; Argentina

BACKGROUND & AIMS: Chronic, progressive hepatobiliary disease is the most severe complication of erythropoietic protoporphyria (EPP) and can require liver transplantation, although the mechanisms that lead to liver failure are unknown. We characterized protoporphyrin-IX (PPIX)-linked hepatobiliary disease in BALB/c and C57BL/6 (Fechm1Pas) mice with mutations in ferrochelatase as models for EPP. METHODS: Fechm1Pas and wild-type (control) mice were studied at 12-14 weeks of age. PPIX was quantified; its distribution in the liver, serum levels of lipoprotein-X, liver histology, contents of bile salt and cholesterol phospholipids, and expression of genes were compared in mice of the BALB/c and C57BL/6 backgrounds. The in vitro binding affinity of PPIX for bile components was determined. RESULTS: Compared with mice of the C57BL/6 background, BALB/c Fechm1Pas mice had a more severe pattern of cholestasis, fibrosis with portoportal bridging, bile acid regurgitation, sclerosing cholangitis, and hepatolithiasis. In C57BL/6 Fechm1Pas mice, PPIX was sequestrated mainly in the cytosol of hepatocytes and Kupffer cells, whereas, in BALB/c Fechm1Pas mice, PPIX was localized within enlarged bile canaliculi. Livers of C57BL/6 Fechm1Pas mice were protected through a combination of lower efflux of PPIX and reduced synthesis and export of bile acid. CONCLUSIONS: PPIX binds to bile components and disrupts the physiologic equilibrium of phospholipids, bile acids, and cholesterol in bile. This process might be involved in pathogenesis of sclerosing cholangitis from EPP; a better understanding might improve diagnosis and development of reagents to treat or prevent liver failure in patients with EPP.

BACKGROUND & AIMS: Chronic, progressive hepatobiliary disease is the most severe complication of erythropoietic protoporphyria (EPP) and can require liver transplantation, although the mechanisms that lead to liver failure are unknown. We characterized protoporphyrin-IX (PPIX)-linked hepatobiliary disease in BALB/c and C57BL/6 (Fechm1Pas) mice with mutations in ferrochelatase as models for EPP. METHODS: Fechm1Pas and wild-type (control) mice were studied at 12-14 weeks of age. PPIX was quantified; its distribution in the liver, serum levels of lipoprotein-X, liver histology, contents of bile salt and cholesterol phospholipids, and expression of genes were compared in mice of the BALB/c and C57BL/6 backgrounds. The in vitro binding affinity of PPIX for bile components was determined. RESULTS: Compared with mice of the C57BL/6 background, BALB/c Fechm1Pas mice had a more severe pattern of cholestasis, fibrosis with portoportal bridging, bile acid regurgitation, sclerosing cholangitis, and hepatolithiasis. In C57BL/6 Fechm1Pas mice, PPIX was sequestrated mainly in the cytosol of hepatocytes and Kupffer cells, whereas, in BALB/c Fechm1Pas mice, PPIX was localized within enlarged bile canaliculi. Livers of C57BL/6 Fechm1Pas mice were protected through a combination of lower efflux of PPIX and reduced synthesis and export of bile acid. CONCLUSIONS: PPIX binds to bile components and disrupts the physiologic equilibrium of phospholipids, bile acids, and cholesterol in bile. This process might be involved in pathogenesis of sclerosing cholangitis from EPP; a better understanding might improve diagnosis and development of reagents to treat or prevent liver failure in patients with EPP.

Moringa oleifera Lam. (Moringaceae) is a medicinally important plant, used as traditional medicine all over the world particularly in South Asia and India. Hydroalcoholic (50% v/v) root extract of M. oleifera (150 mg/kg, p.o.) with piperine (2.5 mg/kg, p.o), or curcumin (5.0 mg/kg, p.o.) was administered daily for 1 week in Female Wistar albino rats against beryllium toxicity (1.0 mg/kg, i.p. daily for 5 weeks). Beryllium altered hepatorenal function and enhanced the leakage of AST, ALT, and LDH, depleted SALP activity, and increased the level of urea, uric acid, creatinine, triglyceride and total cholesterol in the blood. Beryllium altered tissue biochemical parameters by a decrease in SDH, ALPase, ATPase activities, and increased ACPase activity, depleted hemoglobin and ALAD activity with an increase in ALAS activity and serum bilirubin. A significant amount of beryllium deposited in the liver, kidney, spleen, and bones. M. oleifera with curcumin showed better antitoxic potential ...

Chemical and biological hazards may have serious implications on the exposed individuals and a wealth of quality-ensured guidance and information for health care workers is available on the internet. Harmful chemicals can get into the body if you breathe, eat, or drink them or if they are absorbed through the skin. Study group was 20-person Exposure to Occupational Chemicals in chemistry department at Koya university for more than 5 years. In addition, the study includes 20 subject as control group in this study. The blood was drawn into test tubes to estimation of lipid profile, liver parameters, kidney function tests and heavy metal. Full automatic chemical analyzer (Cobas C311) was used to determine the biochemical parameters and atomic absorption was used to estimate the heavy metals. The results showed significant decrease in ALT, AST, albumin and triglyceride, and non-significant difference in total protein, total bilirubin, cholesterol, urea, creatinine, uric acid, Hg and Pb in case group as compared to control group.

In photodynamic therapy (PDT), a noninvasive anticancer treatment, visible light, is used as a magic bullet selectively destroying cancer cells by a photosensitizer that is nontoxic in the dark. Protoporphyrin IX (PpIX) is a natural photosensitizer synthesized in the cell, which is also a chelating agent that if bonded to Fe 2+ forms heme, a central component of hemoglobin. Therefore, xenobiotic iron chelators can disturb iron homeostasis, increasing the accumulation of PpIX, obstructing the last step of heme biosynthesis, and enhancing PDT efficiency. However, the attempts to use this promising idea have not proved to be hugely successful. Herein, we revisited this issue by analyzing the application of iron chelators highly toxic in the dark, which should have higher Fe 2+ affinity than the nontoxic chelators used so far. We have designed and prepared thiosemicarbazones (TSC) with the highest dark cellular cytotoxicity among TSCs ever reported. We demonstrate that compound 2 exerts powerful PDT enhancement when used in combination with 5-aminolevulinic acid (ALA), a precursor of PpIX.

The aim of this study was to estimate the activity of superoxide dismutase (SOD) and catalase in erythrocytes and malondialdehyde (MDA) in plasma of battery manufacturing workers (BMW) of Western Maharashtra (India) who were occupationally exposed to lead (Pb) over a long period of time (about 15 years). This study was also aimed to determine the Pb intoxication resulted in a disturbance of heme biosynthesis in BMW group. The blood Pb level of BMW group (n = 28) was found to be in the range of 25.8-78.0 µg/dL (mean + SD, 53.63 + 16.98) whereas in Pb unexposed control group (n = 35) the range was 2.8-22.0 µg/dL (mean + SD, 12.52 + 4.08). The blood level (Pb-B) and urinary lead level (Pb-U) were significantly increased in BMW group as compared to unexposed control. Though activated d-aminolevulinic acid dehydratase (ALAD) activities in BMW group did not show any significant change when compared to control group but activated / non activated erythrocyte-ALAD activities in BMW group showed a significant increase. Erythrocyte-zinc protoporphyrin (ZPP), urinary daminolevulinic acid (ALA-U) and porphobilinogen (PBG-U) of BMW groups elevated significantly as compared to control. A positive correlation (r = 0.66, p< 0.001) between Pb-B and ALA-U were found in BMW group but no such significant correlation (r = 0.02, p> 1.0) were observed in control group. Hematological study revealed a significant decrease of hemoglobin concentration, packed cell volume (%) and other blood indices and a significant increase of total leucocytes count in BMW group in comparison to control group. The serum MDA content was significantly increased (p< 0.001) and the activities of antioxidant enzymes such as erythrocyte-SOD (p< 0.001) and erythrocytecatalase (p< 0.001) were significantly reduced in BMW group as compared to control group. A positive correlation (r = 0.45, p<0.02) between Pb-B and serum MDA level was observed in BMW group (Pb-B range 25.8-78.0 µg / dL) but such significant correlation did not notice in control group (Pb-B range 2.8-22.0 µg / dL).The study clearly showed an adverse effect of heme biosynthesis and imbalance of pro-oxidant / antioxidant status in lead exposed battery manufacturing workers resulting in increase in lipid peroxidation associated with decrease in erythrocyte-SOD and erythrocyte-catalase activities.

The aim of this study was to estimate the activity of superoxide dismutase (SOD) and catalase in erythrocytes and malondialdehyde (MDA) in plasma of battery manufacturing workers (BMW) of Western Maharashtra (India) who were occupationally exposed to lead (Pb) over a long period of time (about 15 years). This study was also aimed to determine the Pb intoxication resulted in a disturbance of heme biosynthesis in BMW group. The blood Pb level of BMW group (n = 28) was found to be in the range of 25.8-78.0 µg/dL (mean + SD, 53.63 + 16.98) whereas in Pb unexposed control group (n = 35) the range was 2.8-22.0 µg/dL (mean + SD, 12.52 + 4.08). The blood level (Pb-B) and urinary lead level (Pb-U) were significantly increased in BMW group as compared to unexposed control. Though activated d-aminolevulinic acid dehydratase (ALAD) activities in BMW group did not show any significant change when compared to control group but activated / non activated erythrocyte-ALAD activities in BMW group showed a significant increase. Erythrocyte-zinc protoporphyrin (ZPP), urinary daminolevulinic acid (ALA-U) and porphobilinogen (PBG-U) of BMW groups elevated significantly as compared to control. A positive correlation (r = 0.66, p< 0.001) between Pb-B and ALA-U were found in BMW group but no such significant correlation (r = 0.02, p> 1.0) were observed in control group. Hematological study revealed a significant decrease of hemoglobin concentration, packed cell volume (%) and other blood indices and a significant increase of total leucocytes count in BMW group in comparison to control group. The serum MDA content was significantly increased (p< 0.001) and the activities of antioxidant enzymes such as erythrocyte-SOD (p< 0.001) and erythrocytecatalase (p< 0.001) were significantly reduced in BMW group as compared to control group. A positive correlation (r = 0.45, p<0.02) between Pb-B and serum MDA level was observed in BMW group (Pb-B range 25.8-78.0 µg / dL) but such significant correlation did not notice in control group (Pb-B range 2.8-22.0 µg / dL).The study clearly showed an adverse effect of heme biosynthesis and imbalance of pro-oxidant / antioxidant status in lead exposed battery manufacturing workers resulting in increase in lipid peroxidation associated with decrease in erythrocyte-SOD and erythrocyte-catalase activities.

In photodynamic therapy (PDT), a noninvasive anticancer treatment, visible light, is used as a magic bullet selectively destroying cancer cells by a photosensitizer that is nontoxic in the dark. Protoporphyrin IX (PpIX) is a natural photosensitizer synthesized in the cell, which is also a chelating agent that if bonded to Fe 2+ forms heme, a central component of hemoglobin. Therefore, xenobiotic iron chelators can disturb iron homeostasis, increasing the accumulation of PpIX, obstructing the last step of heme biosynthesis, and enhancing PDT efficiency. However, the attempts to use this promising idea have not proved to be hugely successful. Herein, we revisited this issue by analyzing the application of iron chelators highly toxic in the dark, which should have higher Fe 2+ affinity than the nontoxic chelators used so far. We have designed and prepared thiosemicarbazones (TSC) with the highest dark cellular cytotoxicity among TSCs ever reported. We demonstrate that compound 2 exerts powerful PDT enhancement when used in combination with 5-aminolevulinic acid (ALA), a precursor of PpIX.

The aim of this study was to estimate the activity of superoxide dismutase (SOD) and catalase in erythrocytes and malondialdehyde (MDA) in plasma of battery manufacturing workers (BMW) of Western Maharashtra (India) who were occupationally exposed to lead (Pb) over a long period of time (about 15 years). This study was also aimed to determine the Pb intoxication resulted in a disturbance of heme biosynthesis in BMW group. The blood Pb level of BMW group (n = 28) was found to be in the range of 25.8-78.0 µg/dL (mean + SD, 53.63 + 16.98) whereas in Pb unexposed control group (n = 35) the range was 2.8-22.0 µg/dL (mean + SD, 12.52 + 4.08). The blood level (Pb-B) and urinary lead level (Pb-U) were significantly increased in BMW group as compared to unexposed control. Though activated d-aminolevulinic acid dehydratase (ALAD) activities in BMW group did not show any significant change when compared to control group but activated / non activated erythrocyte-ALAD activities in BMW group showed a significant increase. Erythrocyte-zinc protoporphyrin (ZPP), urinary daminolevulinic acid (ALA-U) and porphobilinogen (PBG-U) of BMW groups elevated significantly as compared to control. A positive correlation (r = 0.66, p< 0.001) between Pb-B and ALA-U were found in BMW group but no such significant correlation (r = 0.02, p> 1.0) were observed in control group. Hematological study revealed a significant decrease of hemoglobin concentration, packed cell volume (%) and other blood indices and a significant increase of total leucocytes count in BMW group in comparison to control group. The serum MDA content was significantly increased (p< 0.001) and the activities of antioxidant enzymes such as erythrocyte-SOD (p< 0.001) and erythrocytecatalase (p< 0.001) were significantly reduced in BMW group as compared to control group. A positive correlation (r = 0.45, p<0.02) between Pb-B and serum MDA level was observed in BMW group (Pb-B range 25.8-78.0 µg / dL) but such significant correlation did not notice in control group (Pb-B range 2.8-22.0 µg / dL).The study clearly showed an adverse effect of heme biosynthesis and imbalance of pro-oxidant / antioxidant status in lead exposed battery manufacturing workers resulting in increase in lipid peroxidation associated with decrease in erythrocyte-SOD and erythrocyte-catalase activities.

Moringa oleifera Lam. (Moringaceae) is a medicinally important plant, used as traditional medicine all over the world particularly in South Asia and India. Hydroalcoholic (50% v/v) root extract of M. oleifera (150 mg/kg, p.o.) with piperine (2.5 mg/kg, p.o), or curcumin (5.0 mg/kg, p.o.) was administered daily for 1 week in Female Wistar albino rats against beryllium toxicity (1.0 mg/kg, i.p. daily for 5 weeks). Beryllium altered hepatorenal function and enhanced the leakage of AST, ALT, and LDH, depleted SALP activity, and increased the level of urea, uric acid, creatinine, triglyceride and total cholesterol in the blood. Beryllium altered tissue biochemical parameters by a decrease in SDH, ALPase, ATPase activities, and increased ACPase activity, depleted hemoglobin and ALAD activity with an increase in ALAS activity and serum bilirubin. A significant amount of beryllium deposited in the liver, kidney, spleen, and bones. M. oleifera with curcumin showed better antitoxic potential ...

The aim of this study was to estimate the activity of superoxide dismutase (SOD) and catalase in erythrocytes and malondialdehyde (MDA) in plasma of battery manufacturing workers (BMW) of Western Maharashtra (India) who were occupationally exposed to lead (Pb) over a long period of time (about 15 years). This study was also aimed to determine the Pb intoxication resulted in a disturbance of heme biosynthesis in BMW group. The blood Pb level of BMW group (n = 28) was found to be in the range of 25.8-78.0 µg/dL (mean + SD, 53.63 + 16.98) whereas in Pb unexposed control group (n = 35) the range was 2.8-22.0 µg/dL (mean + SD, 12.52 + 4.08). The blood level (Pb-B) and urinary lead level (Pb-U) were significantly increased in BMW group as compared to unexposed control. Though activated d-aminolevulinic acid dehydratase (ALAD) activities in BMW group did not show any significant change when compared to control group but activated / non activated erythrocyte-ALAD activities in BMW group showed a significant increase. Erythrocyte-zinc protoporphyrin (ZPP), urinary daminolevulinic acid (ALA-U) and porphobilinogen (PBG-U) of BMW groups elevated significantly as compared to control. A positive correlation (r = 0.66, p< 0.001) between Pb-B and ALA-U were found in BMW group but no such significant correlation (r = 0.02, p> 1.0) were observed in control group. Hematological study revealed a significant decrease of hemoglobin concentration, packed cell volume (%) and other blood indices and a significant increase of total leucocytes count in BMW group in comparison to control group. The serum MDA content was significantly increased (p< 0.001) and the activities of antioxidant enzymes such as erythrocyte-SOD (p< 0.001) and erythrocytecatalase (p< 0.001) were significantly reduced in BMW group as compared to control group. A positive correlation (r = 0.45, p<0.02) between Pb-B and serum MDA level was observed in BMW group (Pb-B range 25.8-78.0 µg / dL) but such significant correlation did not notice in control group (Pb-B range 2.8-22.0 µg / dL).The study clearly showed an adverse effect of heme biosynthesis and imbalance of pro-oxidant / antioxidant status in lead exposed battery manufacturing workers resulting in increase in lipid peroxidation associated with decrease in erythrocyte-SOD and erythrocyte-catalase activities.

The aim of this study was to estimate the activity of superoxide dismutase (SOD) and catalase in erythrocytes and malondialdehyde (MDA) in plasma of battery manufacturing workers (BMW) of Western Maharashtra (India) who were occupationally exposed to lead (Pb) over a long period of time (about 15 years). This study was also aimed to determine the Pb intoxication resulted in a disturbance of heme biosynthesis in BMW group. The blood Pb level of BMW group (n = 28) was found to be in the range of 25.8-78.0 µg/dL (mean + SD, 53.63 + 16.98) whereas in Pb unexposed control group (n = 35) the range was 2.8-22.0 µg/dL (mean + SD, 12.52 + 4.08). The blood level (Pb-B) and urinary lead level (Pb-U) were significantly increased in BMW group as compared to unexposed control. Though activated d-aminolevulinic acid dehydratase (ALAD) activities in BMW group did not show any significant change when compared to control group but activated / non activated erythrocyte-ALAD activities in BMW group showed a significant increase. Erythrocyte-zinc protoporphyrin (ZPP), urinary daminolevulinic acid (ALA-U) and porphobilinogen (PBG-U) of BMW groups elevated significantly as compared to control. A positive correlation (r = 0.66, p< 0.001) between Pb-B and ALA-U were found in BMW group but no such significant correlation (r = 0.02, p> 1.0) were observed in control group. Hematological study revealed a significant decrease of hemoglobin concentration, packed cell volume (%) and other blood indices and a significant increase of total leucocytes count in BMW group in comparison to control group. The serum MDA content was significantly increased (p< 0.001) and the activities of antioxidant enzymes such as erythrocyte-SOD (p< 0.001) and erythrocytecatalase (p< 0.001) were significantly reduced in BMW group as compared to control group. A positive correlation (r = 0.45, p<0.02) between Pb-B and serum MDA level was observed in BMW group (Pb-B range 25.8-78.0 µg / dL) but such significant correlation did not notice in control group (Pb-B range 2.8-22.0 µg / dL).The study clearly showed an adverse effect of heme biosynthesis and imbalance of pro-oxidant / antioxidant status in lead exposed battery manufacturing workers resulting in increase in lipid peroxidation associated with decrease in erythrocyte-SOD and erythrocyte-catalase activities.

Sickle cell anemia (SCA) is an inherited disorder of hemoglobin synthesis, characterized by life-long severe hemolytic anemia and vasoocclussive crisis. Oxidative stress play important role in pathophysiology of sickle cell anaemia. Therefore, the study was undertaken to evaluate the levels of plasma lipid peroxidation product malondialdehyde (MDA), plasma total antioxidant capacity, erythrocytic activity of superoxide dismutase and catalase. We found significantly elevated plasma MDA level and activity of erythrocytic superoxide dis-mutase. While plasma total antioxidant capacity and activity of erythrocytic catalase were reduced significantly in SCA patients. These observations provide the evidence of imbalance between oxidant and antioxidant status leading to chronic oxidative stress.

6-Aminolaevulinic acid dehydratase activity is traditionally accepted as the most sensitive measurable biological index of lead toxicity. We have measured 6-aminolaevulinic acid dehydratase activity and blood lead concentration in 47 healthy controls (A), 42 iron deficient patients (B) and 38 occupationally exposed to lead subjects (C). Blood lead levels [% (SD)] did not differ between groups A and B [051 (0.21) and 0.43 (0.19) pmol L-I, respectively] while those of group C [2.28 (0.56) pmolL-I were significantly higher (P < 0.001) as compared to the controls. 6-Aminolaevulinic acid dehydratase activity zyxwvut [X (SD)] was significantly increased [3599 (1909) pmol L-I h-'1 in group B and decreased in group C [lo52 (532) pmol L-I h-I] as compared to the controls [2034 (446) pmol L-1 h-I]

The aim of this study was to estimate the activity of superoxide dismutase (SOD) and catalase in erythrocytes and malondialdehyde (MDA) in plasma of battery manufacturing workers (BMW) of Western Maharashtra (India) who were occupationally exposed to lead (Pb) over a long period of time (about 15 years). This study was also aimed to determine the Pb intoxication resulted in a disturbance of heme biosynthesis in BMW group. The blood Pb level of BMW group (n = 28) was found to be in the range of 25.8 -78.0 µg/dL (mean + SD, 53.63 + 16.98) whereas in Pb unexposed control group (n = 35) the range was 2.8 -22.0 µg/dL (mean + SD, 12.52 + 4.08). The blood level (Pb-B) and urinary lead level (Pb-U) were significantly increased in BMW group as compared to unexposed control. Though activated d-aminolevulinic acid dehydratase (ALAD) activities in BMW group did not show any significant change when compared to control group but activated / non activated erythrocyte -ALAD activities in BMW group showed a significant increase. Erythrocyte-zinc protoporphyrin (ZPP), urinary daminolevulinic acid (ALA-U) and porphobilinogen (PBG-U) of BMW groups elevated significantly as compared to control. A positive correlation (r = 0.66, p< 0.001) between Pb-B and ALA-U were found in BMW group but no such significant correlation (r = 0.02, p> 1.0) were observed in control group. Hematological study revealed a significant decrease of hemoglobin concentration, packed cell volume (%) and other blood indices and a significant increase of total leucocytes count in BMW group in comparison to control group. The serum MDA content was significantly increased (p< 0.001) and the activities of antioxidant enzymes such as erythrocyte-SOD (p< 0.001) and erythrocytecatalase (p< 0.001) were significantly reduced in BMW group as compared to control group. A positive correlation (r = 0.45, p<0.02) between Pb-B and serum MDA level was observed in BMW group (Pb-B range 25.8 -78.0 µg / dL) but such significant correlation did not notice in control group (Pb-B range 2.8 -22.0 µg / dL).The study clearly showed an adverse effect of heme biosynthesis and imbalance of pro-oxidant / antioxidant status in lead exposed battery manufacturing workers resulting in increase in lipid peroxidation associated with decrease in erythrocyte-SOD and erythrocyte-catalase activities.

Sažetak Napravljeno je retrospektivno ispitivanje koje je obuhvatilo 60 radnika profesionalno izloženih anorganskomu olovu te skupinu od 60 kontrolnih ispitanika. Ispitivanje se temeljilo na posebnome upitniku o izloženosti olovu i procjeni toksičnoga ...

This paper describes a retrospective cohort study comparing 60 workers occupationally exposed to inorganic lead and 60 matched controls. All subjects were assessed using data obtained from a specially designed Questionnaire for lead exposure and toxic effects assessment, physical examination, spirometry, ECG, and laboratory tests including blood lead level (BLL) and biomarkers of lead toxic effects. Muscle pain, droopiness, and work-related nasal symptoms were significantly more frequent in lead workers. The prevalence of lung symptoms was higher in lead workers than in controls, but not significantly (20 % vs. 6.6 %, respectively). Mean values of BLL and δ-aminolevulinic acid (ALA) were significantly higher in lead workers. The activity of δ-aminolevulinic acid dehydratase (ALAD) in lead workers was significantly lower than in controls. Abnormal of BLL, ALAD, and ALA were more frequent in lead workers, with statistical difference for BLL and ALAD. Inverse correlation was found between BLL and ALAD, and positive correlation between BLL and age, years of employment, and years of exposure. Inverse correlation was found between ALAD and age, years of employment, years of exposure, blood pressure, alcohol consumption, and years of alcohol consumption. Changes in spirometry correlated inversely with BLL. A positive correlation was found between BLL and erythrocyte count and haemoglobin concentration, whereas it was inverse for ALAD and haemoglobin concentration. A significant difference was found for BLL and ALAD, with a very high odds ratio (14.64 and 7.23, respectively) and high relative risk (4.18 and 3.08, respectively). Our data have confirmed the association between occupational lead exposure and deviation in specific biological markers of lead effect and between the role of occupational exposure in the development of adverse effects.

The aim of this study was to estimate the activity of superoxide dismutase (SOD) and catalase in erythrocytes and malondialdehyde (MDA) in plasma of battery manufacturing workers (BMW) of Western Maharashtra (India) who were occupationally exposed to lead (Pb) over a long period of time (about 15 years). This study was also aimed to determine the Pb intoxication resulted in a disturbance of heme biosynthesis in BMW group. The blood Pb level of BMW group (n = 28) was found to be in the range of 25.8 -78.0 µg/dL (mean + SD, 53.63 + 16.98) whereas in Pb unexposed control group (n = 35) the range was 2.8 -22.0 µg/dL (mean + SD, 12.52 + 4.08). The blood level (Pb-B) and urinary lead level (Pb-U) were significantly increased in BMW group as compared to unexposed control. Though activated d-aminolevulinic acid dehydratase (ALAD) activities in BMW group did not show any significant change when compared to control group but activated / non activated erythrocyte -ALAD activities in BMW group showed a significant increase. Erythrocyte-zinc protoporphyrin (ZPP), urinary daminolevulinic acid (ALA-U) and porphobilinogen (PBG-U) of BMW groups elevated significantly as compared to control. A positive correlation (r = 0.66, p< 0.001) between Pb-B and ALA-U were found in BMW group but no such significant correlation (r = 0.02, p> 1.0) were observed in control group. Hematological study revealed a significant decrease of hemoglobin concentration, packed cell volume (%) and other blood indices and a significant increase of total leucocytes count in BMW group in comparison to control group. The serum MDA content was significantly increased (p< 0.001) and the activities of antioxidant enzymes such as erythrocyte-SOD (p< 0.001) and erythrocytecatalase (p< 0.001) were significantly reduced in BMW group as compared to control group. A positive correlation (r = 0.45, p<0.02) between Pb-B and serum MDA level was observed in BMW group (Pb-B range 25.8 -78.0 µg / dL) but such significant correlation did not notice in control group (Pb-B range 2.8 -22.0 µg / dL).The study clearly showed an adverse effect of heme biosynthesis and imbalance of pro-oxidant / antioxidant status in lead exposed battery manufacturing workers resulting in increase in lipid peroxidation associated with decrease in erythrocyte-SOD and erythrocyte-catalase activities.