Lead Organ and Tissue Toxicity: Roles of Mitigating Agents (Part 1)

Lead is one of the metals whose toxicological effect in humans and animals is of clinical concerned as reported by researchers. Quite a number of chemical agents have been reported to ameliorate lead associated toxicological effects especially in animal studies. This literary study reviewed reported toxicological effect of lead on the liver, kidney and brain with emphasis on the roles of mitigating chemical agents. In this review it was observed that his to patho logical changes in lead associated he patotoxicity include hepatomegaly with necrosis, formation of hyper plastic nodules and presence of in tranu clear inclusion bodies within hepatocytes. In the kidney reports revealed various degenerative changes with focal tubular necrosis invaded by inflammatory cells in cortical renal tubules, diminution in the amount of filtration slits, apoptosis in epithelial cells of the glomeruli, increase in lysosomal structures, pinocytic vesicles and large mitochondria in proximal tubule cells. Lead altered mRNA levels of the following apoptotic and neurotrophic factors: caspase 2 and 3 and brain-derived neurotrophic factor in the brain. Histopathological changes occurred in gray matter, anterior cingulate cortex, hippocampus and cerebellum of treated animals. Lead exposure altered biomarkers of liver, kidney and brain function with increased lipid peroxidation and decrease antioxidants function. Lead induced toxicities were observed to be mitigated by vitamin C, vitamin E, calcium, magnesium dimercaptosuccinic acid, calcium disodium ethyl diaminetetra acetic acid and selenium. Extracts of plant origin and chemical substances of animal origin were also reported to mitigate these toxicities. One of the commonly reported mechanisms associated with lead toxicological effect is the generation of Reactive Oxygen Species in organs and tissues this may be supported by the mitigating effect of some antioxidants on lead toxicological effects.