Shirmard Leila Rezaie, Shabani Mohammad, Moghadam Amin Ashena, Zamani Nasim, Ghanbari Hadi, Salimi Ahmad
Department of Pharmaceutics, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.
Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, P.O. Box: 56189-53141, Ardabil, Iran.
Cardiovasc Toxicol. 2022 Jul;22(7):663-675. doi: 10.1007/s12012-022-09750-w. Epub 2022 May 14.
Mitochondrial dysfunction may lead to cardiomyocyte death in trastuzumab (TZM)-induced cardiotoxicity. Accordingly, this study was designed to evaluate the mitochondrial protective effects of curcumin, chrysin and thymoquinone alone in TZM-induced cardiotoxicity in the rats. Forty-eight male adult Wistar rats were divided into eight groups: control group (normal saline), TZM group (2.5 mg/kg I.P. injection, daily), TZM + curcumin group (10 mg/kg, I.P. injection, daily), TZM + chrysin (10 mg/kg, I.P. injection, daily), TZM + thymoquinone (0.5 mg/kg, I.P. injection, daily), curcumin group (10 mg/kg, I.P. injection, daily), chrysin group (10 mg/kg, I.P. injection, daily) and thymoquinone group (10 mg/kg, I.P. injection, daily). Blood and tissue were collected on day 11 and used for assessment of creatine phosphokinase, lactate dehydrogenase (LDH), troponin, malondialdehyde (MDA) amount, glutathione levels and mitochondrial toxicity parameters. TZM increased mitochondrial impairments (reactive oxygen species formation, mitochondrial swelling, mitochondrial membrane potential collapse and decline in succinate dehydrogenase activity) and histopathological alterations (hypertrophy, enlarged cell, disarrangement, myocytes degeneration, infiltration of fat in some areas, hemorrhage and focal vascular thrombosis) in rat heart. As well as TZM produced a significant increase in the level of CK, LDH, troponin, MDA, glutathione disulfide. In most experiments, the co-injection of curcumin, chrysin and thymoquinone with TZM restored the level of CK, LDH, troponin, MDA, GSH, mitochondrial impairments and histopathological alterations. The study revealed the cardioprotective effects of curcumin, chrysin and thymoquinone against TZM-induced cardiotoxicity which could be attributed to their antioxidant and mitochondrial protection activities.
线粒体功能障碍可能导致曲妥珠单抗（TZM）诱导的心脏毒性中的心肌细胞死亡。因此，本研究旨在评估姜黄素、白杨素和百里醌单独对TZM诱导的大鼠心脏毒性的线粒体保护作用。48只成年雄性Wistar大鼠分为八组：对照组（生理盐水）、TZM组（腹腔注射2.5mg/kg，每日一次）、TZM+姜黄素组（腹腔注射10mg/kg，每日一次）、TZM+白杨素组（腹腔注射10mg/kg，每日一次）、TZM+百里醌组（腹腔注射0.5mg/kg，每日一次）、姜黄素组（腹腔注射10mg/kg，每日一次）、白杨素组（腹腔注射10mg/kg，每日一次）和百里醌组（腹腔注射10mg/kg，每日一次）。在第11天采集血液和组织，用于评估肌酸磷酸激酶、乳酸脱氢酶（LDH）、肌钙蛋白、丙二醛（MDA）含量、谷胱甘肽水平和线粒体毒性参数。TZM增加了大鼠心脏的线粒体损伤（活性氧形成、线粒体肿胀、线粒体膜电位崩溃和琥珀酸脱氢酶活性下降）和组织病理学改变（肥大、细胞增大、排列紊乱、心肌细胞变性、某些区域脂肪浸润、出血和局灶性血管血栓形成）。此外，TZM使CK、LDH、肌钙蛋白、MDA、谷胱甘肽二硫化物水平显著升高。在大多数实验中，姜黄素、白杨素和百里醌与TZM联合注射可恢复CK、LDH、肌钙蛋白、MDA、GSH水平、线粒体损伤和组织病理学改变。该研究揭示了姜黄素、白杨素和百里醌对TZM诱导的心脏毒性的心脏保护作用，这可能归因于它们的抗氧化和线粒体保护活性。
