Background Myocardial injury is considered as a worldwide main cause of morbidity and mortality. The present study aimed to investigate the probable cardioprotective activity of the naturally occurring endogenous fatty acid ester methyl palmitate (MP) against isoproterenol (ISO)-induced myocardial injury in rats and the possible underlying molecular mechanisms. The study was carried out in two consecutive sets of experiments; the first set screened the cardioprotective dose of MP in ISO-intoxicated rats. In the second set, forty male Sprague Dawley rats received either MP (150 mg/kg, p.o) three times/week for 2 weeks and/or 2 consecutive doses of ISO separated by 24 h (85 mg/kg, s.c) on the 13th and 14th days. Different cardiotoxicity and oxidative stress markers were assessed. Furthermore, endothelial nitric oxide synthase (eNOS) levels were determined. For detection of apoptosis, Bax, Bcl-2, and caspase 3 were estimated. To assess inflammation, toll-like receptor 4 (TLR-4) and tumor necrosis factor-alpha (TNF-α) were measured using ELISA. Meanwhile, nuclear factor kappa B (NF-kB) and cyclooxygenase-2 (COX-2) were detected immunohistochemically. Results Pretreatment with MP significantly ameliorated the cardiotoxicity and oxidative stress markers. It also markedly elevated eNOS content, decreased apoptotic marker expression, and mitigated TLR-4 activation and other inflammatory markers. Electrocardiography and histopathological examination also confirmed the cardioprotective effect of MP. Conclusion The findings of this study indicated that MP possesses a potent cardioprotective activity against ISO-induced myocardial injury through its significant antioxidant, anti-apoptotic, anti-inflammatory, and vasodilatation activities. Graphical abstract

Cardioprotective agents are compounds that provide heart protection and decrease cardiotoxicity incidence. Cardiotoxicity is a serious condition that results in diminishing the heart's ability to pump blood throughout the body and can be developed into heart failure. Oxidative stress is an important pathogenic event in cardiotoxicity where the generated reactive oxygen species (ROS) cause myocardial cellular destruction. Moreover, apoptosis, fibrosis, and inflammatory cascades play major roles in cardiotoxicity pathogenesis. Recently, much attention has been paid to the cardioprotective effects of natural products. Methyl palmitate (MP) is a naturally occurring methyl ester that can be also synthesized. This review article aimed to elucidate the potential cardioprotective effects of MP as well as the underlying possible mechanisms. Indeed, MP showed effective cytoprotective roles in various experimental models. In this regard, MP showed potent antioxidant activity which was proven by the decreased production of oxidative stress markers and the increased activity of the endogenous antioxidant enzymes. It also exhibited anti-inflammatory activity which was evidenced by the reduced expression of the pro-inflammatory cytokines and the elevated expression of the anti-inflammatory cytokines. Moreover, MP showed anti-apoptotic activity evidenced by the elevated anti-apoptotic protein expression and the mitigated pro-apoptotic protein expression. Besides, further studies proved the anti-fibrotic and vasodilatation activities of MP. Thus, MP could provide major cardioprotective activities through its antioxidant, anti-inflammatory, anti-apoptotic, anti-fibrotic, and vasodilatation properties.