Prevention of acute adriamycin cardiotoxicity by dantrolene in rats.
Possible preventive effect of dantrolene against the peroxidative damage in rat heart which was induced by the administration of an acute dose of adriamycin (ADR, 20 mg/kg, i.p.) has been examined. Forty-eight hours after ADR administration, biochemical changes including the activities of serum creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) and the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in heart tissue were measured. Pretreatment of rats with dantrolene, given i.p. 30 min prior to ADR injection, substantially reduced the peroxidative damage in the myocardium, and markedly lowered the serum CK-MB, LDH and AST. The protective effects obtained by dantrolene administration, however, were not complete and did not reach those of the control group. Dantrolene, at 5 mg/kg, was useful to obtain significant protective effects, while the protector effect of higher dantrolene dosing level (10 mg/kg) was weak or absent. These results suggest that, at least in part, due to antioxidative properties, dantrolene may provide a significant protective effect against acute ADR-induced cardiotoxicity.
Büyükokuroğlu
Mehmet Emin
ME
Department of Pharmacology, Atatürk University, Faculty of Medicine, Erzurum, Turkey. memin@atauni.edu.tr
Taysi
Seyithan
S
Buyukavci
Mustafa
M
Bakan
Ebubekir
E
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D009202:Cardiomyopathies / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D003402:Creatine Kinase / Q000097:blood; D003620:Dantrolene / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D005979:Glutathione Peroxidase / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009125:Muscle Relaxants, Central / Q000008:administration & dosage / Q000627:therapeutic use*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D009125:Muscle Relaxants, Central; D008315:Malondialdehyde; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D003402:Creatine Kinase; D003620:Dantrolene