Nomega-nitro-L-arginine methylester ameliorates myocardial toxicity induced by doxorubicin.
The effects of Nomega-nitro-L-arginine methylester (L-NAME) and L-arginine on cardiotoxicity that is induced by doxorubicin (Dox) were investigated. A single dose of Dox 15 mg/kg i.p. induced cardiotoxicity, manifested biochemically by a significant elevation of serum creatine phosphokinase (CPK) activity [EC 2.7.3.2]. Moreover, cardiotoxicity was further confirmed by a significant increase in lipid peroxides, measured as malon-di-aldehyde (MDA) in cardiac tissue homogenates. The administration of L-NAME 4 mg/kg/d p.o. in drinking water 5 days before and 3 days after the Dox injection significantly ameliorated the cardiotoxic effects of Dox, judged by the improvement in both serum CPK activity and lipid peroxides in the cardiac tissue homogenates. On the other hand, the administration of L-arginine 70 mg/kg/d p.o. did not protect the cardiac tissues against the toxicity that was induced by the Dox treatment. The findings of this study suggest that L-NAME can attenuate the cardiac dysfunction that is produced by the Dox treatment via the mechanism(s), which may involve the inhibition of the nitric oxide (NO) formation. L-NAME may, therefore, be a beneficial remedy for cardiotoxicity that is induced by Dox and can then be used to improve the therapeutic index of Dox.
Mansour
Mahmoud Ahmed
MA
Department of Pharmacology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. mansour1960us@yahoo.com
El-Din
Ayman Gamal
AG
Nagi
Mahmoud N
MN
Al-Shabanah
Othman A
OA
Al-Bekairi
Abdullah M
AM
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D003402:Creatine Kinase / Q000096:biosynthesis / Q000097:blood; D004317:Doxorubicin / Q000633:toxicity*; D004790:Enzyme Induction; D004952:Esters; D006321:Heart / Q000187:drug effects*; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D051379:Mice; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D004952:Esters; D008054:Lipid Peroxides; D019335:Nitroarginine; D004317:Doxorubicin; D003402:Creatine Kinase