The effects of N-acetylcysteine on cisplatin-induced cardiotoxicity on isolated rat hearts after short-term global ischemia

Abstract

© 2015 The Authors. The aim of this study was to estimate the protective effect of N-acetyl- l-cysteine (NAC) against cisplatin-induced cardiotoxicity under conditions of ischemic-reperfusion injury. Wistar albino rats were randomly divided into three groups (n=8): control, cisplatin (5mg/kg/w, i.p., 5 weeks) and cisplatin+NAC group (cisplatin - 5mg/kg/w, i.p. and NAC - 500mg/kg/w, i.p., 5 weeks). Isolated hearts were perfused according to the modified Langendorff technique at constant pressure (70cmH<inf>2</inf>O). Following cardiodynamic parameters were measured: maximum rate of left ventricular pressure development, minimum rate of left ventricular pressure development, left ventricular systolic pressure (SLVP), left ventricular diastolic pressure and heart rate. The ischemic vasodilation episodes were induced by the complete interruption of coronary inflow for 30, 60 and 120s. The samples of the coronary venous effluent (CVE) were continuously collected during the reperfusion period for determination of coronary flow (CF) rate and oxidative stress markers (H<inf>2</inf>O<inf>2</inf>, O<inf>2</inf>^-, NO<inf>2</inf>^- and thiobarbituric acid reactive substances - TBARS).Cisplatin reduced CF, heart rate and overflow (total, maximal and duration of overflow) during reperfusion, and increased SLVP (under basal conditions and after global ischemias). Cisplatin increased levels of H<inf>2</inf>O<inf>2</inf> (under basal conditions), O<inf>2</inf>^- and TBARS (under basal conditions and after ischemia), but decreased NO<inf>2</inf>^- levels (during reperfusion) in CVE, and decreased superoxide dismutase and reduced glutathione in serum. NAC attenuated cisplatin-induced changes of cardiodynamic parameters (except CF under basal conditions) and oxidative stress parameters.Those results suggest that NAC, by decreasing oxidative stress, may be useful in cardioprotection during cisplatin therapy.