Protective effect of N-acetylcysteine on cyclophosphamide-induced cardiotoxicity in rats.
Cyclophosphamide (CP) is an oxazaphosphorine nitrogen mustard alkylating drug used for the treatment of chronic and acute leukemias, lymphoma, myeloma, and cancers of the breast and ovary. It is known to cause severe cardiac toxicity. This study investigated the protective effect of N-Acetylcysteine (NAC) on CP-induced cardiotoxicity in rats. CP resulted in a significant increase in serum aminotransferases, creatine kinase (CK), lactate dehydrogenase(LDH) enzymes, asymmetric dimethylarginine and tumor necrosis factor-α and significant decrease in total nitrate/nitrite(NOx). In cardiac tissues, a single dose of CP (200mg/kg, i.p.) resulted in significant increase in malondialdehyde and NOx and a significant decrease in reduced glutathione content, glutathione peroxidase, catalase, and superoxide dismutase activities. Interestingly, Administration of NAC (200mg/kg, i.p.) for 5 days prior to CP attenuates all the biochemical changes induced by CP. These results revealed that NAC attenuates CP-induced cardiotoxicity by inhibiting oxidative and nitrosative stress and preserving the activity of antioxidant enzymes.
Health Radiation Research Department, National Center for Radiation Research and Technology, PO Box 29, Nasr City, Cairo, Egypt. Electronic address: hebahosny@hotmail.com.
Heba H
HH
Mansour
Health Radiation Research Department, National Center for Radiation Research and Technology, PO Box 29, Nasr City, Cairo, Egypt.
Shereen M
SM
El Kiki
Radiation Biology Department, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt.
Hesham F
HF
Hasan
D000111:Acetylcysteine / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D066126:Cardiotoxicity / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D003520:Cyclophosphamide / Q000009:adverse effects*; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D009569:Nitric Oxide; D008315:Malondialdehyde; D003520:Cyclophosphamide; D000111:Acetylcysteine
ADMA; Cardiotoxicity; Cyclophosphamide; N-acetylcysteine; Nitric oxide; Oxidative stress