Protective effect of low molecular weight heparin on oxidative injury and cellular abnormalities in adriamycin-induced cardiac and hepatic toxicity.
The aim of the present work is to evaluate the effect of a heparin derivative, low molecular weight heparin (LMWH) on the biochemical changes, tissue peroxidative damage and abnormal antioxidant levels in adriamycin (ADR) induced cardiac and hepatic toxicity. Male Wistar rats (140 +/- 10 g) were divided into four groups: untreated control (group I), ADR group (a single dose intravenous injection of 7.5 mg/kg ADR--group II), LMWH control (300 microg/day per rat s.c. for 1 week--group III) and ADR plus LMWH group (7.5 mg/kg ADR on day 1 of study period followed by LMWH treatment, 300 microg/day per rat commencing on day 8 and continued for a week. At the end of the 2-week experimental period, all animals were terminated. Cellular damage was assessed in terms of serum and tissue lactate dehydrogenase (LDH), aminotransferases and alkaline phosphatase (ALP) activities. Creatine phosphokinase (CPK) was assessed in the serum and heart tissue. The role of LMWH in altering the oxidative stress in ADR-induced toxicity was evaluated on the basis of its influence on cardiac and hepatic lipid peroxidation and antioxidant status (enzymatic and non-enzymatic)--superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx), reduced glutathione (GSH), alpha-tocopherol (Vitamin E) and ascorbate (Vitamin C). LMWH administration to ADR-induced rats prevented the rise in serum and tissue levels of LDH, aminotransferases and ALP, while these parameters were significantly elevated in the ADR group in comparison with the control group. Cardiotoxicity indicated by rise in serum CPK in the ADR group was attenuated by LMWH treatment in group IV. LMWH decreased the cardiac and hepatic lipid peroxidation induced by ADR. Histologic examination revealed that the ADR-induced deleterious changes in the heart and liver tissues were offset by LMWH treatment. Restoration of cellular normalcy accredits LMWH with cytoprotective role in adriamycin-induced cardiac and hepatic toxicity.
Deepa
P R
PR
Department of Medical Biochemistry, Dr ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai 600113, India.
Varalakshmi
P
P
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity*; D000925:Anticoagulants / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity*; D004359:Drug Therapy, Combination; D004798:Enzymes / Q000097:blood; D005609:Free Radicals / Q000378:metabolism; D006331:Heart Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D007275:Injections, Intravenous; D008107:Liver Diseases / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000903:Antibiotics, Antineoplastic; D000925:Anticoagulants; D004798:Enzymes; D005609:Free Radicals; D006495:Heparin, Low-Molecular-Weight; D008315:Malondialdehyde; D004317:Doxorubicin