Lead induced impairments in brain mitochondrial metabolic and oxidative enzymes in pregnant and non-pregnant rats: protective effect of α-tocopherol

Our earlier studies showed that exposure to lead (Pb) caused irreversible perturbations in the cholinergic system and neurobehavioral functions of female rats. In this study, we extended our studies to investigate the role of mitochondrial metabolic and oxidative enzymes in response to Pb exposure in pregnant and non-pregnant rats. Further, we evaluated the protective effect of α-tocopherol against Pb-induced mitochondrial dysfunction in female rats. Pregnant (GD 1 to PND 21) and non-pregnant rats were exposed to 0.2% Pb for the period of 42 days (6 weeks) while alpha (α)-tocopherol (100 mg/kg) was given orally through gavage for a period of 21 days (last 3 weeks) to Pb exposed pregnant and non-pregnant rats. Rats were decapitated on 7th day and 30th-day after the 42 days Pb exposure. Pb exposure decreased the activities of mitochondrial succinate dehydrogenase (SDH), isocitrate dehydrogenase (ICDH), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) enzymes whereas the glucose-6-phosphate dehydrogenase (G6PDH), and malondialdehyde (MDA) levels increased in the cortex, cerebellum, and hippocampus at both 7th and 30th day points of pregnant and non-pregnant rats. Pb-induced alterations were greater in cortex coinciding with higher Pb levels observed in the cortex than hippocampus and cerebellum. Although the supplementation of α-tocopherol significantly reversed the Pb-induced alterations in the mitochondrial metabolic and oxidative enzymes, the reversal effect on Pb levels in different brain regions was marginal in both pregnant and non-pregnant rats. In conclusion, our data demonstrate that exposure to Pb significantly alters the mitochondrial enzymes in brain region-dependent manner and the effect of Pb was greater in non-pregnant female rats than pregnant rats. Further, the data provide evidence for the protective efficacy of α -tocopherol against Pb-toxicity.