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1.
Hum Exp Toxicol ; 23(3): 129-35, 2004 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15119532

RESUMEN

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.


Asunto(s)
Antibióticos Antineoplásicos/toxicidad , Antioxidantes/farmacología , Doxorrubicina/toxicidad , Eritrocitos/efectos de los fármacos , Estrés Oxidativo , Ácido Tióctico/farmacología , Animales , Antioxidantes/metabolismo , Membrana Eritrocítica/efectos de los fármacos , Membrana Eritrocítica/enzimología , Eritrocitos/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Fragilidad Osmótica/efectos de los fármacos , Oxidación-Reducción/efectos de los fármacos , Ratas , Ratas Wistar
2.
Hum Exp Toxicol ; 22(5): 249-54, 2003 May.
Artículo en Inglés | MEDLINE | ID: mdl-12774887

RESUMEN

The cytoprotective activity of alpha-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 alpha-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 of alpha-lipoic acid and its cytoprotective action against ADR-induced cardiotoxicity.


Asunto(s)
Antioxidantes/farmacología , Doxorrubicina/antagonistas & inhibidores , Doxorrubicina/toxicidad , Lesiones Cardíacas/inducido químicamente , Lesiones Cardíacas/prevención & control , Peroxidación de Lípido/efectos de los fármacos , Ácido Tióctico/farmacología , Animales , Bovinos , Radicales Libres/antagonistas & inhibidores , Radicales Libres/toxicidad , Lesiones Cardíacas/enzimología , Masculino , Ratas , Ratas Wistar
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