Cardio-protective impact of gabapentin against doxorubicin-induced myocardial toxicity in rats; emphasis on modulation of inflammatory-apoptotic signaling.

International Immunopharmacology
Yara A SamraEman Said

Abstract

Cardiotoxicity is one of the most commonly encountered adverse effects observed alongside the therapeutic use of doxorubicin (DOX), thus curbing its therapeutic utility. The current study was conducted to evaluate the cardioprotective effect of gabapentin (Gaba), a Ca + 2 channel blocker with emerging pharmacological merits, against DOX-induced cardiotoxicity. Gaba was orally administered at two dose levels (10 and 30 mg/kg) for 21 days parallel to DOX injection. DOX induced significant functional, biochemical, and histopathological injury to the myocardium. Gaba treatment revealed a cardioprotective effect as manifested in the significant restoration of electrocardiogram parameters, including the heart rate, ST segment elevation, QRS and T wave amplitudes, and QT and PR intervals. The biomarkers of myocardial injury, namely serum creatine kinase, aspartate aminotransferase, and lactate dehydrogenase activities, significantly declined as well as the concomitant improvement of the myocardial oxidative status. Mechanistically, Gaba treatment significantly reduced the myocardial contents of c-Jun N-terminal kinase (JNK), the major modulator of inflammatory/apoptotic signaling. However, the myocardial contents of the apoptotic biom...Continue Reading

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