Counteracting adriamycin-induced oxidative stress by administration of N-acetyl cysteine and vitamin E.
Adriamycin (ADR), a cytotoxic antineoplastic drug, is used in the treatment of various solid tumors. However, its efficacy continues to be challenged by significant toxicities including nephrotoxicity. In the present study, the effects of N-acetyl cysteine (NAC) and vitamin E, known antioxidants, were investigated on ADR-induced peroxidative damage in rat kidney. Adult male albino rats of Wistar strain were administered ADR as a single dose (10 mg/kg body weight, i.v.). Histopathological studies indicated that ADR-treated kidney sections show focal tubular necrosis and casts. ADR-injected rats showed a significant decline in the activities/levels of enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and glutathione-S-transferase) and non-enzymic antioxidants (thiols, vitamin C and vitamin E) with high malondialdehyde levels. The extent of nephrotoxicity was evident from the increased activities of urinary marker enzymes (alkaline phosphatase, lactate dehydrogenase and gamma-glutamyltransferase). Treatment with NAC and vitamin E (50 mg/kg b.w., i.p.) 1 day prior to ADR administration maintained near normal activities of the enzymes, significantly reduced lipid peroxidation and prevented the necrosis caused by ADR, thereby proving to be an effective thiol replenishing agent and antioxidant.
Kalaiselvi
Periandavan
P
Department of Medical Biochemistry, Dr. ALM. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, India. pkalaiselvi@yahoo.com
Pragasam
Viswanathan
V
Chinnikrishnan
Srinivasan
S
Veena
Coothan Kandaswamy
CK
Sundarapandiyan
Rajaguru
R
Varalakshmi
Palaninathan
P
D000111:Acetylcysteine / Q000008:administration & dosage*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity*; D000975:Antioxidants / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity*; D004347:Drug Interactions; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000008:administration & dosage*
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D014810:Vitamin E; D004317:Doxorubicin; D000111:Acetylcysteine