Human and animal studies have shown that some drugs and chemical agents have potential hepatotoxic effects. The hepatotoxic effect of drugs and some chemical agents is reported to be associated with the generation of reactive oxygen species (ROS). These ROS are reported to be associated with lipid peroxidation in the liver. This mechanism has led to continuous evaluation of the hepatoprotective effect of antioxidants in humans and animals. Among the antioxidants been evaluated is vitamin C which is a water soluble antioxidant. Reports have linked vitamin C with hepatoprotective property in animals and humans. It synergistic hepatoprotective effect with other antioxidants was also reported. Due to these reports a comprehensive literature review on the hepatoprotective property of vitamin C in humans and animals was performed. It was observed that vitamin C exhibited a reputable hepatoprotective effect in humans and animals. Research showed that vitamin C inhibited hepatotoxicity induced by drugs, heavy metals, organophosphate insecticides and some chemical agents. Vitamin C was reported to normalized levels of serum alanine aminotransferase, aspartate aminotransferase, gamma glutamine, alkaline phosphatase, lactate dehydrogenase and malondialdehyde and serum bilirubin in intoxicated animals. It potentiates the activities of free radical scavengers, superoxide dimutase, and catalase glutathione peroxidase thereby preventing microsomal lipid peroxidation, liver fibrosis, liver necrosis and hepatic inflammation. In humans vitamin C was reported to be beneficial in non alcoholic steatohepatitis and in patients with fatty liver disease. Hepatoprotective property of vitamin C is attributed to it antioxidant property. Vitamin C (ascorbic acid) which is a major water-soluble antioxidant is believed to decrease lipid peroxidation either directly or indirectly by regenerating vitamin E. Vitamin C is an important free radical scavenger in extracellular fluids, trapping radicals and protecting biomembranes from peroxide damage. Vitamin C effectively scavenges singlet oxygen, superoxide, hydroxyl, water soluble peroxyl radical and hypochlorous acid. It is also reported to be an excellent source of electrons and therefore can donate electrons to free radicals such as hydroxyl and super oxide radicals and quench their activity. Vitamin C is an essential co-factor involved in many biochemical functions and acts as an electron donor or reducing agent. In this review it is observe that vitamin C has hepatoprotective effect which increases when co administered with other agents precisely antioxidants.

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.

There are increasing reports on cadmium associated hepatotoxicity, due to these reports this study reviewed relevant literature on cadmium associated hepatotoxicity with emphasis on doses, route of administration, salt forms (cadmium compounds) and the roles of mitigating agents. Reports have shown that continuous exposure of the liver to cadmium has led to hepatotoxicity. Humans are generally exposed to cadmium by two main routes, inhalation and ingestion. In this study, evaluation of relevant literature showed that irrespective of route of administration and salt forms cadmium hepatotoxicity is dose and time dependent. Cadmium associated hepatotoxicity manifested through impaired functions of hepatic biomarkers (transaminases), enzymatic and non enzymatic antioxidants. Histopathological damage to liver architecture manifested as swelling of hepatocytes, focal necrosis, hepatocytes degeneration, dilatation of ribosomes, damage of membrane-bounded lysosomes, nuclear pyknosis and cytoplasm vacuolization. Deterioration of mitochondrial cristae, deposition of collagen fibrils, hypertrophy of kuffer cells, congestion in central veins and sinusoids, infiltration of mixed inflammatory cells and peripheral hemorrhage also occurred. Hepatotoxic effect of cadmium was mitigated by Vitamin C, Vitamin E, Manganese (11) Chloride, N-acetylcysteine and Selenium. Extracts of plant origin including Solanum tuberosum, Calycopteris floribunda and Hibiscus sabdariffa mitigated cadmium induced hepatotoxicity. Chemical substances of animal origin including honey and camel milk were reported to have ameliorated cadmium induced hepatotoxicity. One of the mechanisms of cadmium induced hepatotoxicity is reported to be associated with the up regulation of reactive oxygen species (oxidative stress) which caused oxidative damage to lipid contents of membranes and direct liver injury. Conclusion cadmium is dose and time dependently hepatotoxic irrespective of route of administration, salt form and is ameliorated by some antioxidants and extracts of plant and materials of animal origin which may require further evaluation for clinical application.

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