Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
Physiology Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
J Biochem Mol Toxicol. 2019 Mar;33(3):e22253. doi: 10.1002/jbt.22253. Epub 2018 Oct 28.
Alcohol consumption is a major global risk factor for mortality and morbidity. We aimed to delineate the mechanisms underlying the potential ameliorative effects of hesperidin against chronically ethanol-induced cardiotoxicity. Sixty male albino rats were divided into normal control group, hesperidin-treated control group, untreated alcoholic group, and hesperidin-treated alcoholic group. Transcription factor-EB (TFEB) expression levels were estimated using real-time reverse transcription-polymerase chain reaction. Peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1-α), macrophage inflammatory protein-1 α, poly-(ADP-ribose)-polymerase-1 (PARP-1) activity, and tenascin C levels in cardiac tissues were estimated by enzyme-linked immunosorbent assay; while tissue malondialdehyde and total antioxidant capacity were evaluated spectrophotometrically. Our data portrayed promoting lysosomal biogenesis, as judged by upregulation of TFEB expression and its target PGC1-α, as well as decreased PARP-1 activity and offsetting inflammation, oxidative stress, and tissue injury as the principal culprits mediating the cardioprotective effect of hesperidin in alcohol-induced cardiotoxicity. In conclusion, hesperidin can be used as a cardioprotective agent in chronically ethanol-induced cardiotoxicity.
饮酒是导致全球死亡率和发病率的主要风险因素之一。本研究旨在探讨橙皮苷对慢性乙醇诱导的心脏毒性潜在改善作用的机制。将 60 只雄性白化大鼠分为正常对照组、橙皮苷治疗对照组、未治疗酒精组和橙皮苷治疗酒精组。采用实时逆转录聚合酶链反应估计转录因子-EB(TFEB)的表达水平。通过酶联免疫吸附试验估计心肌组织中过氧化物酶体增殖物激活受体γ共激活因子 1-α(PGC1-α)、巨噬细胞炎症蛋白-1α、多聚(ADP-核糖)-聚合酶 1(PARP-1)的活性和 tenascin C 水平;同时通过分光光度法评估组织丙二醛和总抗氧化能力。我们的数据表明,橙皮苷通过上调 TFEB 表达及其靶基因 PGC1-α,促进溶酶体生物发生,同时降低 PARP-1 活性,并减轻炎症、氧化应激和组织损伤,从而发挥其在慢性乙醇诱导的心脏毒性中的心脏保护作用。综上所述,橙皮苷可作为慢性乙醇诱导的心脏毒性的心脏保护剂。