Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Department of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, P.O. Box 8678-3-65178, Hamadan, Iran.
Oxid Med Cell Longev. 2021 Jan 7;2021:6406318. doi: 10.1155/2021/6406318. eCollection 2021.
This study was undertaken to evaluate the therapeutic potential effect of pentoxifylline (PTX) against arsenic trioxide (ATO)-induced cardiac oxidative damage in mice. Thirty-six male albino mice were divided into six groups and treated intraperitoneally with normal saline (group 1), ATO (5 mg/kg; group 2), PTX (100 mg/kg; group 3), and different doses of PTX (25, 50, and 100 mg/kg; groups 4, 5, and 6, respectively) with ATO. After four weeks, the blood sample was collected for biochemical experiments. In addition, cardiac tissue was removed for assessment of oxidative stress markers and histopathological changes (such as hemorrhage, necrosis, infiltration of inflammatory cells, and myocardial degeneration). The findings showed that ATO caused a significant raise in serum biochemical markers such as lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and troponin-I (cTnI), glucose, total cholesterol (TC), and triglyceride (TG) levels. In addition to histopathological changes in cardiac tissue, ATO led to the significant increase in cardiac lipid peroxidation (LPO) and nitric oxide (NO); remarkable decrease in the activity of cardiac antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx); and the depletion of the total antioxidant capacity (TAC) and total thiol groups (TTGs). PTX was able to reduce the increased levels of serum cardiac markers (LDH, CPK, cTnI, TC, and TG), cardiac LPO, and improve antioxidant markers (TAC, TTGs, CAT, SOD, and GPx) alongside histopathologic changes. However, no significant changes were observed in elevated serum glucose and cardiac NO levels. In conclusion, the current study showed the potential therapeutic effect of PTX in the prevention of ATO-induced cardiotoxicity via reversing the oxidative stress.
这项研究旨在评估己酮可可碱（PTX）对三氧化二砷（ATO）诱导的小鼠心脏氧化损伤的治疗潜力。36 只雄性白化小鼠被分为六组，分别腹腔注射生理盐水（第 1 组）、ATO（5mg/kg；第 2 组）、PTX（100mg/kg；第 3 组）和不同剂量的 PTX（25、50 和 100mg/kg；第 4、5 和 6 组）。四周后，采集血液样本进行生化实验。此外，还取出心脏组织评估氧化应激标志物和组织病理学变化（如出血、坏死、炎性细胞浸润和心肌变性）。结果显示，ATO 导致血清生化标志物如乳酸脱氢酶（LDH）、肌酸磷酸激酶（CPK）和肌钙蛋白 I（cTnI）、葡萄糖、总胆固醇（TC）和甘油三酯（TG）水平显著升高。除心脏组织的组织病理学变化外，ATO 还导致心脏脂质过氧化（LPO）和一氧化氮（NO）显著增加；心脏抗氧化酶如过氧化氢酶（CAT）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）的活性显著降低；总抗氧化能力（TAC）和总巯基（TTGs）耗竭。PTX 能够降低血清心脏标志物（LDH、CPK、cTnI、TC 和 TG）、心脏 LPO 的升高水平，并改善抗氧化标志物（TAC、TTGs、CAT、SOD 和 GPx）以及组织病理学变化。然而，血清葡萄糖和心脏 NO 水平的升高没有观察到显著变化。总之，本研究表明，PTX 通过逆转氧化应激具有预防 ATO 诱导的心脏毒性的潜在治疗作用。
