Influence of a low-molecular-weight heparin derivative on the nitric oxide levels and apoptotic DNA damage in adriamycin-induced cardiac and renal toxicity.
The spectrum of the anti-apoptotic potential of heparin is currently under scrutiny in various tissues and under various pathological situations. In this study, the role of a low-molecular-weight heparin derivative (LMWH), certoparin in adriamycin-induced oxidative DNA damage has been evaluated in the cardiac and renal tissues. Two groups of male albino rats of the Wistar strain (140+/-10 g) received a single intravenous injection of adriamycin (7.5mg/kg), and one of them received low-molecular-weight heparin (Certoparin Sodium, 300 microg/day/rat s.c.) treatment, commencing on day 8, continued for a week. The nitrosative stress in ADR cytotoxicity is indicated by the 1.51-fold cardiac and 2.36-fold renal increase in reactive nitrogen species (RNS), while LMWH treatment restores normalcy (p<0.001). The influence of LMWH on the pro-inflammatory and pro-apoptotic cytokine, TNF-alpha was studied. Renal and cardiac levels of TNF-alpha showed a significant rise (p<0.001) in the ADR cytotoxic group, while the TNF-alpha values departed towards control levels in the LMWH treated group (p<0.001). DNA damage indicated by the fragmentation pattern (agarose gel electrophoresis) and the significantly increased comet tail length (p<0.001) observed after alkaline single cell gel electrophoresis confirmed the toxicity induced by ADR on DNA in the untreated group. In the LMWH-treated group, the observation of intact DNA band after agarose gel electrophoresis, and the finding of comet tail length being comparable with that of the control substantiated the protection rendered by the LMWH, certoparin. In short, the results suggest that the low-molecular-weight heparin derivative, certoparin exerts beneficial effects on the nitrosative status, and on the biological macromolecules as DNA and curtails the rise of the pro-apoptotic and pro-inflammatory cytokine, TNF-alpha in the cardiac and renal tissues.
Deepa
P R
PR
Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai 600113, India. dipa_pr@mailcity.com
Varalakshmi
P
P
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D000925:Anticoagulants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D053938:DNA Fragmentation / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity*; D004587:Electrophoresis, Agar Gel; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006331:Heart Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D009573:Nitrites; D026361:Reactive Nitrogen Species; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D004317:Doxorubicin