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. 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. 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.

中文翻译：

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天然组织守护者棕榈酸甲酯对异丙肾上腺素诱发的大鼠心肌的假定的抗炎，抗氧化和抗凋亡作用

心肌损伤被认为是世界范围内发病率和死亡率的主要原因。本研究旨在调查天然存在的内源性脂肪酸酯棕榈酸甲酯（MP）对大鼠异丙肾上腺素（ISO）引起的心肌损伤的可能的心脏保护活性，以及​​可能的潜在分子机制。该研究是在连续的两组实验中进行的。第一组筛选了在ISO醉酒的大鼠中MP的心脏保护剂量。在第二组中，四十只雄性Sprague Dawley大鼠每周两次接受MP（150 mg / kg，口服）3次，持续2周，和/或在连续的24h内分别接受2小时连续剂量的ISO，间隔24 h（85 mg / kg，sc）。第13和14天。评估了不同的心脏毒性和氧化应激指标。此外，确定了内皮一氧化氮合酶（eNOS）水平。为了检测细胞凋亡，估计了Bax，Bcl-2和caspase 3。为了评估炎症，使用ELISA测量了Toll样受体4（TLR-4）和肿瘤坏死因子-α（TNF-α）。同时，免疫组织化学检测了核因子κB（NF-kB）和环氧合酶-2（COX-2）。MP预处理可显着改善心脏毒性和氧化应激指标。它还显着提高eNOS含量，减少凋亡标记物的表达，并减轻TLR-4激活和其他炎症标记物。心电图和组织病理学检查也证实了MP的心脏保护作用。这项研究的结果表明，MP通过显着的抗氧化剂，抗凋亡，抗炎，抗氧化剂，抗ISO诱导的心肌损伤作用，具有强大的心脏保护活性。