Arsenic Exposure from Drinking Water Disrupts Hepatic DNA Integrity and Alters Energy Metabolism in Lymphocytes and Brain Tissue

Background: Arsenic contamination of underground drinking water has become a major global environmental concern. Studies have linked the consumption of water contaminated by arsenic to myriads of disease outcomes through unknown mechanisms. Methods: In the present study, the possible effects of varying concentrations of arsenic added to drinking water were on energy- metabolizing enzymes (hexokinase, aldolase, lactate dehydrogenase, malate dehydrogenase, Complex I, Complex II, Complex III, and Complex IV) in the lymphocytes and brains of male albino rats. Periodic acid Schiff stain and Feulgen reaction techniques were also used to assess hepatic glycogen level and the possibility of hepatic DNA damage, respectively. Male Wistar rats (n=45) were exposed to arsenic added to drinking water at 100, 150, and 200 ppm for 4, 8, and 12 weeks. Rats in the control group (n=5) received distilled water. At the end of the experimental period, blood was taken via cardiac puncture, and the brain and liver were also excised for biochemical and histological studies. Results: Exposure to arsenic resulted in significant (p < 0.05) body weight loss with a concomitant increase in the relative brain and liver weights. A significant time- and dose-dependent (p < 0.05) inhibition of the activities of lymphocyte hexokinase and aldolase, lymphocyte and brain malate dehydrogenase, as well as complexes I, II, III, IV in both the lymphocyte and brain was the hallmark of arsenic exposure. Histological studies indicated that arsenic exposure also led to the depletion of hepatic glycogen storage in the liver and marked DNA damage in the arsenic-exposed animals relative to control. Conclusion: These findings indicate that arsenic perturbed the activities of energy-metabolizing enzymes, which may be one mechanism of arsenic-induced toxicity.