The effect of 4-phenylbutyric acid on isoproterenol induced myocardial infarction in rat

Abstract

Introduction: Chaperone mediated autophagy (CMA) is one of the intracellular pathways which eliminates unnecessary and damaged cellular components through lysosomal enzymes. 4-phenyl butyric acid (4-PBA) is a chemical chaperone that could induce CMA. Aim: The aim of this study was to investigate the effect of 4-PBA on hemodynamic parameters, biochemical factors, inflammation and histopathological changes on Isoproterenol (ISO) induced myocardial infarction (MI) in rat heart tissue. Methods and Materials: In this study male wistar rats weighing 270-300 g were housed at 25-27 ° C on a 12-h light/dark cycle. Isoproterenol was injected subcutaneously (sc) at first and second days for induction of acute MI. Treatment groups were received intraperitoneal 4-PBA (20, 40, 80 mg/kg/day) for 5 days (day 1 to 5). On the sixth day hemodynamic parameters were recorded and analyzed. Also histopathological changes, peripheral neutrophil count and biochemical factors were measured. Results: The results showed that ISO administration induced significant cardiac injuries and hemodynamic depression while these damages improved by 4-PBA administration (P <0.05). Treatment with 4-PBA reduced peripheral neutrophils count in comparison to ISO group (P <0.05). Histopathological analysis showed a significant attenuation of ISO induced cardiomyocyte destruction by 4-PBA. In biochemical factors total antioxidant capacity was significantly increased by 4-PBA administration (P <0.05); however, changes in other biochemical factors including Lactate dehydrogenase and Malondialdehyde were not considerable. Conclusion: This study showed that 4-PBA has cardioprotective effects against ISO-induced MI injuries. This protection is probably related to CMA induction and reduction of endoplasmic reticulum stress.