Abstract
Kaempferol (KMP), a dietary flavonoid, has antioxidant, anti-inflammatory, and antiapoptotic effects. Hence, we investigated the effect of KMP in ischemia-reperfusion (IR) model of myocardial injury in rats. We studied male albino Wistar rats that were divided into sham, IR-control, KMP-20 + IR, and KMP 20 per se groups. KMP (20 mg/kg; i.p.) was administered daily to rats for the period of 15 days, and, on the 15th day, ischemia was produced by one-stage ligation of left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. After completion of surgery, rats were sacrificed; heart was removed and processed for biochemical, morphological, and molecular studies. KMP 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-α, IL-6, and NFκB), inhibition of active JNK and p38 proteins, and activation of ERK1/ERK2, a prosurvival kinase. Additionally, it also attenuated apoptosis by reducing the expression of proapoptotic proteins (Bax and Caspase-3), TUNEL positive cells, and increased level of antiapoptotic proteins (Bcl-2). In conclusion, KMP protected against IR injury by attenuating inflammation and apoptosis through the modulation of MAPK pathway.
Highlights
Myocardial infarction (MI) results from sudden obstruction of blood supply to a part of the heart resulting in ischemia and death of the affected cardiac tissue
We have shown that KMP prevents the development and progression of IR injury and improves cardiac performance, primarily through the activation of ERK1/ERK2 and suppression of p38/jun N-terminal kinase (JNK)/TNFα/NF-κBp65 pathway
It is well established that reperfusion of the ischemic tissue causes increased generation of oxygen rich-free radicals that disrupt balance between oxidants and antioxidants leading to uncontrolled myocardial injury
Summary
Myocardial infarction (MI) results from sudden obstruction of blood supply to a part of the heart resulting in ischemia and death of the affected cardiac tissue. Studies have demonstrated that activation of ERK1/ERK2 and inhibition of p38/JNK protect the myocardium from IR injury by reducing oxidative stress and inflammation and by maintaining cytoskeletal architecture [1, 7]. An in vitro study, the protective role of KMP in anoxia/reoxygenation injury via the inhibition of oxidative stress and apoptosis, was demonstrated [14]. Considerable evidence shows that KMP exerts its anti-inflammatory and cardioprotective activities by modulating MAPK pathway [8, 15]. With the background that p38, JNK, and ERK1/ERK2 play important roles in IR injury and KMP has modulating effect on these proteins, we undertook this study to investigate whether KMP has cardioprotective effect in IR injury and if so, whether it is mediated through MAPK pathway
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