Rutin trihydrate attenuated cisplatin- induced cardiac toxicity in isolated perfused rat’s hearts

Background The present study aims to investigate the protective effect of rutin against cisplatin induced toxic effects on the mechanical performance of the myocardium, histopathology, and oxidative stress in isolated perfused rat hearts. Methods Cardiotoxicity of cisplatin was assessed at three dosage levels (1, 7, and 14 mg/l) in the isolated perfused rat hearts. The toxic effect of cisplarin was assessed on left ventricular pressure (LVP), heart rate (HR), dp/dt(max), dp/dt (min), perfusion pressure, pressure-time index, contractility index and duration of diastole. Measurements were carried out one minute before perfusion of cisplatin and 60 minutes after perfusion. Results Cisplatin reduced significantly (p < 0.05) in a dose-dependent manner LVP, dp/dt(max), dp/dt(min) and pressure- time index. Perfusion of rutin trihydrate (1 µM/l), 10 minutes before administration of cisplatin and throughout the experiment significantly (p < 0.05) attenuated the detrimental effects of cisplatin on cardiac parameters. Cisplatin caused degeneration and necrosis of cardiac muscle cells, while rutin reduced these changes and restored normal heart histology. Moreover, cisplatin reduced the myocardium concentration of reduced glutathione and increased the level of malondialdehyde, whereas rutin almost reversed these changes. Conclusion Cisplatin-induced dose-dependent impairment of several parameters of cardiac function and produced histopathological alterations in isolated rat hearts. These harmful effects of cisplatin were ameliorated by rutin trihydrate. These findings suggest the potential protective effects of rutin trihydrate against cisplatin-induced cardiotoxicity.

The Effect of Hawthorn Extract on Coronary Flow

Hawthorn extract has been used for heart failure and may decrease cardiac cell injury and improve cardiac function. One proposed mechanism for hawthorn action is vasodilation. We hypothesized that hawthorn extract would increase coronary blood flow in isolated perfused rat hearts. Coronary flow was measured in nonworking perfused rat hearts (Langendorff, constant pressure) using a flow probe; data were collected electronically in real time. Hawthorn extract showed an early (30-120 seconds) vasodilation, followed by a later (3-5 minutes) decrease in coronary flow. Maximum vasodilation occurred with 240 μg/mL hawthorn extract. Hawthorn’s pattern of activity was unlike that of several known vasoactive drugs. Both nitric oxide synthase inhibitors and indomethacin abolished early vasodilation, but they had no effect on the late phase decrease in flow. We suggest that a hawthorn-induced increase in nitric oxide generation leads to an increase in prostacyclin production, thus causing early phase vasodilation.