Hepatotoxic and neurotoxic effects of combined lead and di-(2-ethylhexyl) phthalate exposure: Activation of total -, Ca2+- and Na+K+- ATPases in the liver of male rats

Abstract

Lead and di-(2-ethylhexyl) phthalate (DEHP) are common environmental toxicants of concern around the world. Although effects of individual exposures to both agents are well documented, there is a dearth of information on the effects of co-exposure to both agents. In this study, combined exposure to lead and DEHP was investigated for effects on ATPase activities in the liver, brain and kidney tissues of rats. Male albino rats were daily exposed to either 200 ppm lead as lead acetate in their drinking water and/or 100 mg DEHP kg-1 body weight in olive oil by gastric intubation for 30 days. Changes in total body weight, relative organ weights as well as brain, hepatic and renal activities of total, Na+K+ -, Ca2+ - and Mg2+-ATPases were used as biomarkers of toxicity. Hepatomegaly and brain atrophy heralded exposure to both agents. Individual exposure to lead and DEHP resulted in reduction in hepatic Ca2+- and Mg2+- ATPase activities but no significant effect on total ATPase activity, however combined exposure produced significant activation of Ca2+-, Na+K+- and total ATPase while restoring Mg2+ - ATPase towards control. A potentiating effect on lead by DEHP was observed in hepatic Na+K+ - ATPase. Lead stimulated the activities of renal Ca2+- and total ATPases while DEHP on the contrary caused significant reduction in total ATPase activity and no significant effects on Ca2+- ATPase activity. Co-treatment produced antagonistic effects leading to normal renal Ca2+- and total ATPase activities. Brain Na+K+ -, Ca2+ - and total ATPase activities were depressed in co-exposure while Mg2+ - ATPase was up-regulated. Lead potentiated DEHP-induced inhibition of brain total - ATPase while co-treatment produced antagonistic effects on brain Ca2+ - ATPase. The findings of this study highlight organ specific variations in response to combined lead and DEHP exposure in rats. Key words: Hepatotoxic, neurotoxic, ATPases, DEHP, lead, co-exposure, hepatomegaly.