Oluwatosin Dosumu

Erythrocyte acetylcholinesterase activity as a surrogate indicator of lead-induced neurotoxicity in occupational lead exposure in Abeokuta, Nigeria

Dose-effect and dose-response relationships in occupational neurotoxicology are rarely studied by means of biochemical methods. In order to investigate the potential neurotoxic effects of lead during occupational exposure to this metal, the activity of erythrocyte acetylcholinesterase (AcChE), as well as blood pressure and pulse, were determined in various artisans in Abeokuta, Nigeria, who have been shown to be occupationally exposed to lead, and these were related to blood lead levels. AcChE activity in the artisans was inhibited to varying extents. While AcChE activity was inhibited to the tune of 39% in the male petrol station attendants, the inhibition amounted to 32% in female petrol station attendants. In other artisans, AcChE inhibition ranged from 31% in the welders to 38% in painters. The lowest inhibition of 15% was obtained in the panel beaters. Correlations, as calculated by Pearsons method, revealed a significant (p<0.001) inverse linear relationship between AcChE activity and blood lead levels (r=-0.40; y=-120.38x+13935.59; p<0.001). Blood pressure and pulse were not significantly different between control and lead-exposed subjects. Our findings suggest that erythrocyte AcChE activity could be used as a biomarker of lead-induced neurotoxicity in occupationally exposed subjects.

Biomarkers of lead exposure in petrol station attendants and auto-mechanics in Abeokuta, Nigeria: effect of 2-week ascorbic acid supplementation

In order to study the ameliorative effects of ascorbic acid in chronic lead poisoning, petrol station attendants and auto-mechanics in Abeokuta, Nigeria, who have been shown to be occupationally exposed to lead and university students (serving as control), were supplemented daily with 500mg ascorbic acid for 2 weeks. Blood and urine samples were collected from the subjects before and after ascorbic acid regimen and analysed for lead and biochemical effects associated with lead toxicity. The 2-week ascorbic acid supplementation resulted in a significant (P < 0.05) reduction in blood lead in the occupationally exposed subjects. The reduction in blood lead amounted to 57% in male petrol station attendants, 50% in female petrol station attendants and 44% in the auto-mechanics. Urinary excretion of lead increased remarkably in the occupationally exposed subjects (P < 0.05). The biochemical effects associated with the toxic effects of lead also responded positively to the ascorbic acid regimen. Plasma and urine aminolevulinic acid (ALA) were reduced significantly (P < 0.05) by as much as 55% and 57% respectively. Plasma calcium also increased significantly (P < 0.05) in the subjects. Decreased levels of reduced glutathione (GSH) and hemoglobin observed in the occupationally exposed subjects were reversed by ascorbic acid. Glutathione-S-transferase (GST) and catalase (CAT) activities were not affected. Our findings indicate that ascorbic acid may be useful as an economical and convenient prophylactic agent for lead poisoning.

Paraoxonase 1 activity in subchronic low-level inorganic arsenic exposure through drinking water.

Epidemiological evidences indicate close association between inorganic arsenic exposure via drinking water and cardiovascular diseases. While the exact mechanism of this arsenic‐mediated increase in cardiovascular risk factors remains enigmatic, epidemiological studies indicate a role for paraoxonase 1 (PON1) in cardiovascular diseases. To investigate the association between inorganic arsenic exposure and cardiovascular diseases, rats were exposed to sodium arsenite (trivalent; 50, 100, and 150 ppm As) and sodium arsenate (pentavalent; 100, 150, and 200 ppm As) in their drinking water for 12 weeks. PON1 activity towards paraoxon (PONase) and phenylacetate (AREase) in plasma, lipoproteins, hepatic, and brain microsomal fractions were determined. Inhibition of PONase and AREase in plasma and HDL characterized the effects of the two arsenicals. While the trivalent arsenite inhibited PONase by 33% (plasma) and 46% (HDL), respectively, the pentavalent arsenate inhibited the enzyme by 41 and 34%, respectively. AREase activity was inhibited by 52 and 48% by arsenite, whereas the inhibition amounted to 72 and 67%, respectively by arsenate. The pattern of inhibition in plasma and HDL indicates that arsenite induced a dose‐dependent inhibition of PONase whereas arsenate induced a dose‐dependent inhibition of AREase. In the VLDL + LDL, arsenate inhibited PONase and AREase while arsenite inhibited PONase. In the hepatic and brain microsomal fractions, only the PONase enzyme was inhibited by the two arsenicals. The inhibition was more pronounced in the hepatic microsomes where a 70% inhibition was observed at the highest dose of pentavalent arsenic. Microsomal cholesterol was increased by the two arsenicals resulting in increased cholesterol/phospholipid ratios. Our findings indicate that decreased PON1 activity observed in arsenic exposure may be an incipient biochemical event in the cardiovascular effects of arsenic. Modulation of PON1 activity by arsenic may also be mediated through changes in membrane fluidity brought about by changes in the concentration of cholesterol in the microsomes.