Curative Role of D-Penicillamine versus Combined Garlic and Silymarin Extracts on Lead-Induced Nephrotoxicity and Oxidative Stress in Adult Male Albino Rats

Background Lead (Pb) poisoning is still an important global health problem, especially in developing countries. Lead has been extensively used for many years ago, and it will continue to be used in future. Aim of work: This study was conducted to compare the curative role of D-penicillamine versus combined garlic and silymarin extracts for treating nephrotoxicity in adult male rats exposed to Pb for 3 months. Material and methods: The study was conducted on 70 adult male albino rats divided into 7 groups each of 10 rats, where they received all chemicals by oral gavage. Groups I & II were the negative and positive control rats, respectively. Group III received 25 mg/kg/day D-penicillamine for 1 month (4^th month). Group IV received combined garlic 20 mg/kg/day+ silymarin 200 mg/kg/day for 1 month (4^th month). Group V received 20 mg/kg/day Pb acetate for 3 months. Group VI received Pb acetate for 3 months followed by D-penicillamine for another 1 month, with the previously mentioned doses. Group VII received Pb acetate for 3 months followed by combined garlic & silymarin for another 1 month, with the previously mentioned doses. At the end of the experimental period (4 months), Pb-level in blood, urine & kidney tissue, kidney function tests (blood urea and serum creatinine) and serum malondialdehyde (MDA) & glutathione peroxidase (GSH-Px) were measured. Light microscopic examination of hematoxylin and eosin stained kidney tissue was performed to detect histopathological changes. Results: Lead administration significantly elevated blood lead level (BLL), kidney lead level (KLL), urinary lead level (ULL) and malondialdehyde (MDA), while glutathione peroxidase (GSH-Px) showed significant decrease when compared with the negative control rats. In Pb treated group, histopathological examination of the kidney revealed extensive tubular damage by presence of necrotic epithelial cells, tubular degeneration, necrosis, cell swelling, mononuclear cell infiltration, and degenerated organelles.  Kidney functions didn't show any significant differences among all groups. Treatment of rats by D-penicillamine or combined garlic & silymarin extracts resulted in significant decrease in Pb-levels and MDA with a significant increase in blood GSH-PX levels. Also, significant improvement of lead induced histopathological lesions in the kidneys was observed. Combined garlic and silymarin extract treatment showed more significant improvement than D-penicillamine treated Pb-administered groups, in most of the tested parameters. Conclusion: Both D-penicillamine and combined garlic & silymarin extracts can reduce lead induced nephrotoxicity and oxidative stress. Moreover, garlic & silymarin curative effect is better than that of D-penicillamine. Recommendations: Exposure of the population to lead must be controlled. Search for sensitive blood or urinary marker for early detection of kidney damage and further studies are needed to consider a combination of garlic and silymarin is effective in the treatment of lead-induced toxicities.