A17254 Morin ameliorates isoproterenol induced cardiac necrosis in vivo by modulation of oxidative stress, apoptosis and inflammation through of MAPK pathway

Abstract

Objectives: Oxidative stress plays a major role in myocardial injury. Morin, a bioflavonoid has already been investigated for its anti-inflammatory potential in chronic inflammatory conditions. Hence, this study shows the inflammatory mechanisms of Morin against isoproterenol induced myocardial necrosis in rats. Methods: Male Wistar rats were divided into 6 groups (n = 8) i.e. I (normal), II (ISO- control), III, IV, V (morin 20, 40 and 80 respectively) and VI (morin 80 mg/kg per se). Groups III, IV, V and VI were treated orally with daily doses of Morin accordingly. On 26th and 27th day isoproterenol was injected (85 mg/kg s.c.) at 24 h interval to induced myocardial necrosis in group II, III, IV and V. On 28th day hemodynamic parameters were evaluated after anaesthetizing with sodium pentobarbitone (60 mg/kg) from all groups. Then, animals were sacrificed, heart was excised and used for biochemical, histopathological, ultra-structural and immuno-histochemical studies. Tissue was also used for apoptosis and inflammatory markers study through various techniques. Results: In ISO treated rats, there was increase in level of antioxidant enzymes and pro-inflammatory cytokines (TNFα and IL-6). Also, myocardial injury markers like CK-MB and LDH were elevated. On immunohistochemistry, Bax/Bcl-2 ratio was found to be increased. Morin (20/40/80 mg/kg) was observed to improve hemodynamic profile, increased anti-oxidative levels and reduced inflammatory markers and apoptosis. Histopathological and ultrastructural studies demonstrated protective effect in Morin treated group. The immunoblot analysis of MAPK pathway protein supports the anti-inflammatory potential of morin. Conclusion: This study substantiated the beneficial effect of Morin by virtue of anti-oxidative, anti-inflammatory and anti-apoptotic properties. Hence, Morin i