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Combined efficacies of lipoic acid and meso-2,3-dimercaptosuccinic acid on lead-induced erythrocyte membrane lipid peroxidation and antioxidant status in rats

M Nagaraj

Department of Medical Biochemistry, Dr AL Mudaliar Post Graduate Institute of Basic Medical Sciences, University of Madras (Taramani), Chennai-600 113, India

P Varalakshmi

Department of Medical Bio-chemistry, Dr AL Mudaliar Post Graduate Institute of Basic Medical Sciences, University of Madras (Taramani), Chennai-600 113, India; drvlakshmi{at}yahoo.com

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.

Key Words: antioxidants • meso-2,3-dimercaptosuccinic acid • erythrocytes • lead acetate • lipid peroxidation • DL--lipoic acid

Human & Experimental Toxicology, Vol. 22, No. 4, 183-192 (2003)
DOI: 10.1191/0960327103ht335oa


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