Faculty of Medicine, Institute for Treatment and Rehabilitation, University of Niš, Niška Banja, Niš, Serbia.
Institute for Treatment and Rehabilitation, University of Niš, Niška Banja, Niš, Serbia.
Can J Physiol Pharmacol. 2024 Jun 1;102(6):374-382. doi: 10.1139/cjpp-2023-0253. Epub 2023 Dec 11.
Long-term exposure to amiodarone, an antiarrhythmic drug, can induce different organ damage, including liver. Cell damage included by amiodarone is a consequence of mitochondrial damage, reactive oxygen species production, and cell energy depletion leading to programmed cell death. In the present study, hepatoprotective potential of neurohormone melatonin (50 mg/kg/day) was evaluated in a chronic experimental model of liver damage induced by a 4-week application of amiodarone (70 mg/kg/day). The obtained results indicate that amiodarone induces an increase in xanthine oxidase activity, as well as the content of the lipid and protein oxidatively modified products and p53 levels. Microscopic analysis further corroborated the biochemical findings revealing hepatocyte degeneration, apoptosis, and occasional necrosis, with the activation of Kupffer cells. Coadministration of melatonin and amiodaron prevented an increase in certain damage associated parameters, due to its multiple targets. In conclusion, the application of melatonin together with amiodarone prevented an increase in tissue oxidative damage parameters and moderately prevented liver cell apoptosis, indicating that the damage of hepatocytes provoked by amiodarone supersedes the protective properties of melatonin in a given dose.
长期暴露于抗心律失常药物胺碘酮会导致不同器官的损伤，包括肝脏。胺碘酮引起的细胞损伤是线粒体损伤、活性氧物质产生和细胞能量耗竭导致程序性细胞死亡的结果。在本研究中，评估了神经激素褪黑素（50mg/kg/天）在慢性实验性肝损伤模型中的保护作用，该模型是通过 4 周应用胺碘酮（70mg/kg/天）诱导的。研究结果表明，胺碘酮诱导黄嘌呤氧化酶活性增加，以及脂质和蛋白质氧化修饰产物和 p53 水平增加。显微镜分析进一步证实了生化发现，显示肝细胞变性、凋亡和偶尔坏死，伴有枯否细胞的激活。褪黑素和胺碘酮的联合应用可预防某些与损伤相关的参数增加，这是由于其具有多种作用靶点。总之，褪黑素与胺碘酮的联合应用可预防组织氧化损伤参数的增加，并适度预防肝细胞凋亡，表明胺碘酮引起的肝细胞损伤超过了在给定剂量下褪黑素的保护作用。
