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Introduction: Severe industrial diseases result from the hepatic accumulation of mercury, cadmium or chromium in humans and on the other hand cadmium and dichromate and mercuric salts may induce lung or kidney cancer. Acute or chronic CdCl2, HgCl2 or dichromate administration induces hepatic and nephrotoxicity in rodents. Oxidative stress is often cited as a possible cause of metal induced cell death but the death signaling pathways involved have not yet been well investigated.
Method and Materials: To search for death signaling mechanisms we used accelerated cytotoxicity mechanism screening techniques (ACMS) on isolated rat hepatocytes as our cellular model.
Results: Adding the CdC12, HgC12 or K2Cr2O7 to isolated hepatocytes caused a rapid increase in reactive oxygen species ("ROS") formation and a decline in mitochondrial membrane potential. Then lipid per-oxidation and cell-lysis ensued. Cytotoxicity was prevented by "ROS" scavengers and various inhibitors of the mitochondrial permeability transition (MPT) e.g. cyclosporin A, carnitine or trifluoperazine. Antioxidants prevented hepatocyte lysis induced by CdC12 , K2Cr207 but not HgC12.
Conclusion: Hepatocyte lysis was also prevented by various apoptosis inhibitors e.g. cycloheximide, dactinomycin and a tetrapeptide caspase 3 inhibitor which suggested that metal induced hepatocyte lysis involves apoptotic death signals initiated by MPT and "ROS".

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Introduction: Recently depleted uranium is being widely used as anti-armour ammunition and at very high temperature, results in information of an aerosol of very small uranium oxide particles, which may be inhaled. It is alleged that these particles represent a new battlefield hazard because of the chemical toxicology and/or radioactivity.
Method & materials: Male Wistar strain albino rats were divided at random into 3 groups. In the first group normal saline was administrated intraperitioneally (i.p) , this group served as controls. The second group were i.p injected with uranyl acetate 40 mg/kg. In the third group the rats received 100 mg/kg/day silymarin by i.p injection for 5 days and 1hr after the last injection animals were injected with a single i.p dose of uranyl acetate (40 mg/kg). Silymarin was tested for its free radical scavenging activity and protective role against mitochondrial dysfunction in uranyl acetate stressed rats.
Results: Lipid peroxidation activity was increased and activity of mitochondrial enzymes (cytochrome-coxidases, NADH-dehydrogenase, α-ketoglutarate dehydrogenase and succinate dehydrogenase) and glutathione was decreased in the liver and kidney of rats intoxicated with uranyl acetate when compared to control rats. In traperitoneal administration of silymarin significantly reduced the lipid peroxidation, increased the activity of mitochondrial enzymes and increased glutathione to near control level.
Conclusion: These results suggest that the major components in silymarin (including silybin A and B, isosilybin A and B, cis-silybin A and B) play a protective role through their free redical scavenging properties.