PS-B04-7: CHRYSIN AMELIORATES ISOPROTERENOL-INDUCED CARDIAC HYPERTROPHY IN RATS VIA MODULATION OF SIGNALING PATHWAYS

Abstract

Objective: Chrysin, a flavonoid, obtained from honey has shown to possess various pharmacological activities such as anti-oxidant, anti-apoptotic, anti-fibrotic and anti-inflammatory. Isoproterenol (ISO) induced cardiac hypertrophy involve development of oxidative stress, inflammation and fibrosis in the rats. On this basis, the present study was designed to investigate the effect of chrysin in ISO-induced cardiac hypertrophy in rats. Design and method: Male albino Wistar rats were divided into seven groups (n = 6): Normal, ISO-control and chrysin treatment groups (15, 30 and 60 mg/kg; p.o.), chrysin per se (60 mg/kg; p.o.) and combination group (chrysin 60 mg/kg; p.o. + losartan 10 mg/kg; p.o.). Chrysin was administered for the period of 28 days. Hypertrophy in all groups were induced by administration of ISO at the dose of 3 mg/kg; s.c. other than normal and per se groups. On 29th day, rats were anaesthetised, hemodynamic parameters were measured, blood was withdrawn and heart was excised. Heart was stored for the estimation of biochemical, histopathological, ultrastructural, and molecular studies. Results: Chrysin treatment for 28 days significantly improved heart to body weight ratio, normalized hemodynamic parameters, strengthen antioxidant parameters, prevented release of cardiac injury markers and attenuated pathological changes. In addition, it also reduced inflammation (decreased TNF-α, IL-6, pNF-κB/NF-κB ratio), apoptosis (increased Bcl-2 and decreased Bax, caspase-3 and PARP) and fibrosis (decreased TGF-β;/Smad) in ISO-induced hypertrophic rats. Furthermore, it also regulated the expression of various signaling pathways (MAPK, Nrf2/HO-1). All these changes were comparable to the losartan treatment group. Conclusion: Thus, chrysin pre-treatment prevented oxidative stress, inflammation, apoptosis and fibrosis in rats via alteration of various pathways. Hence, chrysin could be further studied for treatment of cardiac hypertrophy.