No abstract

The cytoprotective activity of a-lipoic acid against free radical toxicity manifested during adriamycin (ADR)induced cardiotoxicity has been investigated. ADR is a potent antitumour drug known to cause severe cardiotoxicity. Although ADR generates free radicals, the role of these radicals in the development of cardiac toxicity is still not well understood. In the present study, we evaluated the influence of chronic ADR treatment on the cellular defence mechanism against free radicals and the effect of a-lipoic acid supplementation on ADR-induced cardiotoxicity in male Wistar rats. The increase in lipid peroxidation (LPO) and activities of serum myocardial enzymes, namely lactate dehydrogenase (LDH) and creatinephosphokinase, associated with the decrease in activities of enzymatic (SOD, CAT, GPx, G6PD and GR) and non-enzymatic (GSH, Vit C and Vit E) antioxidants levels were the salient features observed in ADR-induced cardiotoxicity. Lipoic acid pretreated groups showed significant increase in activities of both enzymatic and non-enzymatic antioxidant levels. These observations highlight the antioxidant property ofa-lipoic acid and its cytoprotective action against ADR-induced cardiotoxicity.

One of the most intriguing phenomena observed during adriamycin (ADR) toxicity has been attributed to ADR-induced oxidative stress. The study was aimed to assess the protective effect of lipoic acid (LA) against ADR induced damage to erythrocytes. Male albino rats (Wistar strain) were subjected to ADR (1 mg/kg body weight/day i.v.) once a week for a period of 12 weeks. Haematological indices like haemoglobin levels (Hb) and haematocrit (Ht) were also lowered along with a marked increase in the activities of serum glutamate pyruvate transaminase (SGPT) and serum glutamate oxaloacetate transaminase (SGOT). These rats demonstrated enhanced erythrocyte membrane lipid peroxidation (LPO) and an onslaught in the antioxidant defence armoury, witnessed by lowered activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), vitamin A, vitamin C and vitamin E. Rats administered with ADR showed a marked decline in the activities of membrane-bound ATPases. Abnormal LPO and decreased deformability led to increased osmotic fragility of the red blood cells. Pretreatment with LA (35 mg/kg body weight/day i.p.) 24 hours prior to the administration of ADR once a week for a period of 12 weeks was effective in counteracting these biochemical disturbances, thereby minimizing the toxic side effects of ADR.

This study has highlighted the beneficial effects of LA pretreatment in reversing the damages caused by ADR, by bringing about an improvement in the reductive status of the cell.

Adriamycin widely used in the treatment of neoplastic conditions is nephrotoxic. In the present study the protective effect of lipoic acid was investigated in adriamycin-induced nephrotoxicity in adult male albino Wistar rats. Adriamycin-induced nephrotoxicity was characterized by hyperlipidemia, proteinuria, and hypoproteinemia, by decreased activities of the enzymes N-acetyl-beta-D-glucosaminidase and cathepsin D, by increased lipid peroxidation and decreases in serum catalase and glutathione activities, and by increased urinary and serum urea, creatinine and urinary glycosaminoglycans. Pretreatment with lipoic acid restored the changes, indicating that lipoic acid is renoprotective in adriamycin nephrotoxicity.