P6294-Chlorodiazepam prevents isoproterenol-induced cardiac hypertrophy in rat

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A pathophysiological link exists between oxidative stress and cardiac hypertrophy and its progression to heart failure. In this context, the role of mitochondrial permeability transition pore and translocator protein (TSPO) , which are found to be abundant in the cardiovascular system remains to be investigated. In the present study, we investigated the effect of 4-chorodiazepam (a TSPO ligand) on isoproterenol-induced cardiac hypertrophy in rat. Male Wistar rats (body weight 150-200 g) were administered, isoproterenol (ISO; 5 mg/kg, body weight, subcutaneously) alone or along with 4-chlorodiazepam (4-CD) (0.1 and 0.5 mg/kg, body weight, intraperitoneally) once daily for 14 days. Control rats received normal saline subcutaneously (1ml/kg) for the same duration. ISO-induced increase in heart weight to body weight ratio, left ventricular mass (M-mode echocardiography and gross morphometry) and myocyte size (light microscopy, haematoxylin & eosin stain) were significantly prevented by 4-CD. Hearts of animals with hypertrophy developed significant interstitial fibrosis in histopathology and lipid peroxidation along with decrease in endogenous antioxidants. 4-CD prevented ISO-induced increase in interstitial fibrosis, lipid peroxidation and changes in endogenous antioxidants (Table). In addition 4-chlorodiazepam also prevented ISO-induced β myosin heavy chain expression. In conclusion, this study provides the first evidence of beneficial effects of 4-chlorodiazepam on isoproterenol-induced left ventricular hypertrophy in rat which have implications in defining the strategies for treatment of cardiac hypertrophy.

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