Fisetin, a PPAR gamma agonist improves myocardial injury in rats through Inhibition of MAPK Signalling Pathway mediated oxidative stress and inflammation in Experimental Model of Myocardial Ischemia Reperfusion Injury

[Speaker] Shanky Garg:1
[Co-author] D. S Arya:1, Jagriti Bhattia:1

 Backround: It is well known that oxidative stress and inflammation cause myocardial damage following myocardial ischamia reperfusion (IR) injury. Fisetin, a dietary flavonoid, has antioxida,, antiinflammatory and antiapoptotic effects. Henc,, we investigated the effect of Fisetin in ischemiareperfusion (IR) model of myocardial injury in rats.
Methology: This study was carried out on male albino Wistar rats that were divided into sham, IR-control, Fisetin20 + IR, Fisetin20 + IR +GW and Fisetin 20 per se groups. Fisetin (20 mg/kg; orally) was administered daily to rats for 29 days and on the 29th day, ischemia was produced by one stage ligation of left anterior descending coronary artery for 45 min followed by reperfusion for 60min. After completion of surgery, rats were sacrificed; heart was removed and processed for biochemical, morphological and molecular studies.
Results: Fisetin pretreatment significantly ameliorated IR injury by maintaining cardiac function, normalizing oxidative stress, and preserving morphological alterations. Furthermore, there was a decrease in the level of inflammatory markers (TNF alpha, IL6, and NF kB), inhibition of active JNK and p38 proteins, and activation of ERK1/2, a prosurvival kinase. Additionally, it also attenuated apoptosis by reducing the expression of proapoptotic proteins (Bax and Caspase3), TUNEL positive cells, and increased level of antiapoptotic proteins (Bcl2).
Conclusion: Fisetin protected against IR injury by attenuating inflammation and apoptosis through the modulation of MAPK pathway.
Keywords: Fisetin, Myocardial Infarction, inflammation, oxidative stress.
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