One of the most intriguing phenomenon observed during lead toxicity has been attributed to lead-induced oxidative stress. The combined effect of DL-a-lipoic acid (LA) and meso 2,3-dimercaptosuccinic acid (DMSA) on lead-induced alterations in selected parameters, which are indicators of oxidative stress in erythrocytes, have been studied. Lead acetate (Pb, 0.2%) was administered in drinking water for 5 weeks to induce 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 week 6. Clinical evidence of toxic exposure was evident from the elevated blood lead levels (BPb) along with lowered levels of haemoglobin (Hb) and haematocrit (Ht). Lead-exposed animals showed enhanced membrane lipid peroxidation (LPO) in the erythrocytes. Damage to the erythrocyte membrane was evident from the decline in the activities of the trans-membrane enzymes, viz., Na1, K1 ATPase, Ca21 ATPase and Mg21 ATPase. Lead-exposed rats also suffered an onslaught on the antioxidant defence system witnessed by lowered activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and reduced glutathione (GSH). Serum glutamic-oxoloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) were also elevated in lead-exposed rats. Treatment with either LA or DMSA reversed the lead-induced biochemical disturbances encountered by the erythrocytes, but combined treatment with LA and DMSA was very effective in mitigating all the parameters indicative of oxidative stress.
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.
Lipoic acid (LA) and eicosapentaenoic acid (EPA) have been shown to ameliorate the changes associated with hyperoxaluria. This prompted us to study the effect of EPA-LA, a new derivative, in experimental urolithiatic condition. Foreign body implantation method followed by supple-mentation of ammonium oxalate was adopted to induce stone formation in the bladder. Significant depletion in the antioxidant status was observed in the kidney and bladder of stone-forming animals, associated with increased lipid peroxidation. The present observations provide supporting evidence to the hypothesis that free radicals might be involved in causing toxicity in hyperoxaluric condition. The three drugs, namely LA, EPA and EPA-LA had reversed the above changes, but the effect was more pronounced in EPA-LA-treated stone formers. These features highlight the beneficial effect of EPA-LA wherein the potency of two drugs has been combined. The practical outcome of these findings is that the cellular antioxidant defence can be increased by the supplementation of lipoate and its derivative EPA-LA. Human & Experimental Toxicology (2002) 21, 153–158.
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