Diclofenac sodium, a nonselective nonsteroidal anti-inflammatory drug aggravates doxorubicin-induced cardiomyopathy in rats.
The cardiotoxic effects of selective cyclo-oxygenase-2 inhibitors are well documented. Recently, concerns have been raised over the cardiovascular safety of nonselective nonsteroidal antiinflammatory drugs. The aim of this study was to assess the cardiac effects of diclofenac sodium on doxorubicin-induced cardiomyopathy in rats. Male Wistar rats were treated with doxorubicin (15 mg/kg intraperitoneally, single dose), diclofenac sodium (2.5 and 10 mg/kg/day, respectively, by gavage for 5 days) alone and doxorubicin + diclofenac sodium treatment, 24 hours after doxorubicin administration. Doxorubicin-induced a significant (P < 0.001) increase in the serum lactate dehydrogenase, cardiac thiobarbituric acid-reactive substance and catalase levels and a significant (P < 0.001) decrease in the cardiac glutathione and superoxide dismutase levels, which were significantly (P < 0.001) aggravated by diclofenac sodium treatment. Diclofenac sodium alone also showed a significant change in these parameters compared with the control. Ultrastructural studies showed that doxorubicin causes apoptosis in myocardium, which was characterized by condensation of chromatin network at the margins of nuclear membrane. Apoptosis induced by doxorubicin was exacerbated by diclofenac sodium treatment. Thus, our study indicates that diclofenac sodium, a nonaspirin nonsteroidal anti-inflammatory drug, is not free from cardiotoxicity and aggravates doxorubicin-induced cardiomyopathy in rats.
Singh
Bhulan Kumar
BK
Department of Pharmacology, Hamdard University, New Delhi, India. bhulanpharm@gmail.com
Pathan
Rahila Ahmad
RA
Pillai
Krishna Kolappa
KK
Haque
Syed Ehtaishamul
SE
Dubey
Kiran
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000473:pathology*; D054715:Cardiotoxins / Q000633:toxicity*; D004008:Diclofenac / Q000633:toxicity*; D004317:Doxorubicin / Q000633:toxicity*; D004357:Drug Synergism; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D054715:Cardiotoxins; D004008:Diclofenac; D004317:Doxorubicin