Lipoic acid in combination with a chelator ameliorates lead-induced peroxidative damages in rat kidney.
The deleterious effect of lead has been attributed to lead-induced oxidative stress with the consequence of lipid peroxidation. The present study was designed to investigate the combined effect of DL-alpha-lipoic acid (LA) and meso-2,3-dimercaptosuccinic acid (DMSA) on lead-induced peroxidative damages in rat kidney. The increase in peroxidated lipids in lead-poisoned rats was accompanied by alterations in antioxidant defence systems. Lead acetate (Pb, 0.2%) was administered in drinking water for 5 weeks to induce lead toxicity. LA (25 mg/kg body weight per day i.p.) and DMSA (20 mg/kg body weight per day i.p.) were administered individually and also in combination during the sixth week. Nephrotoxic damage was evident from decreases in the activities of gamma-glutamyl transferase and N-acetyl beta- D-glucosaminidase, which were reversed upon combined treatment with LA and DMSA. Rats subjected to lead intoxication showed a decline in the thiol capacity of the cell, accompanied by high malondialdehyde levels along with lowered activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione metabolizing enzymes (glutathione reductase, glucose-6-phosphate dehydrogenase, glutathione- S-transferase). Supplementation with LA as a sole agent showed considerable changes over oxidative stress parameters. The study has highlighted the combined effect of both drugs as being more effective in reversing oxidative damage by bringing about an improvement in the reductive status of the cell.
Sivaprasad
Rajagopalan
R
Department of Medical Biochemistry, Dr AL Mudaliar Post Graduate Institute of Basic Medical Sciences, University of Madras (Taramani), Chennai 600 113, India.
Nagaraj
Manickam
M
Varalakshmi
Palaninathan
P
D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D002374:Catalase / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007855:Lead Poisoning / Q000188:drug therapy / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D004113:Succimer / Q000494:pharmacology* / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D002614:Chelating Agents; D008054:Lipid Peroxides; D008063:Thioctic Acid; D004113:Succimer; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005723:gamma-Glutamyltransferase; D000118:Acetylglucosaminidase; D005978:Glutathione