Department of Histology and Embryology, Faculty of Medicine, Firat University, Elazig, Turkey.
Department of Midwifery, Faculty of Health Sciences, Mardin Artuklu University, Mardin, Turkey.
Ultrastruct Pathol. 2021 Jan 2;45(1):19-27. doi: 10.1080/01913123.2020.1850964. Epub 2021 Feb 2.
Acetaminophen (APAP)-induced hepatotoxicity is the most common cause of acute liver failure in worldwide. N-acetyl cysteine (NAC) is used as the APAP antidote. Cyclosporin A (CsA) is suppressed mitochondrial damage by binding cyclophilin, a mitochondrial pore transport component. The study aimed to evaluate the effects of NAC, CsA, and NAC+CsA treatments on APAP-induced hepatotoxicity in mice. Mice were randomly divided into five groups (n = 6). 400 mg/kg/ip/single dose APAP, 1200 mg/kg/i.p/single dose NAC and 50 mg/kg/i.p/single dose CsA were performed. Light and electron microscopic alterations were investigated in liver samples. Levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and liver glutathione (GSH) were analyzed. 3-nitrotyrosine and cytochrome c immunoreactivities were evaluated in liver tissue. Here, we found that APAP leads to histopathological and ultrastructural changes in mice liver. Also, APAP increased cytochrome c and 3-nitrotyrosine immunopositive staining. Besides, a significant decrease in liver GSH and an increase in serum AST and ALT levels were detected in the APAP group. Interestingly, NAC+CsA treatment improved histological alterations, cytochrome c, and 3-nitrotyrosine immunoreactivities and liver GSH, serum AST/ALT levels caused by APAP. We suggest that the combination of NAC and CsA reduces acetaminophen-induced hepatotoxicity in mice.
对乙酰氨基酚（APAP）诱导的肝毒性是全世界急性肝衰竭的最常见原因。N-乙酰半胱氨酸（NAC）被用作 APAP 解毒剂。环孢素 A（CsA）通过与线粒体孔道转运成分细胞色素 P450 结合来抑制线粒体损伤。本研究旨在评估 NAC、CsA 和 NAC+CsA 治疗对小鼠 APAP 诱导的肝毒性的影响。将小鼠随机分为五组（n=6）。给予 400 mg/kg/ip/单次剂量 APAP、1200 mg/kg/i.p/单次剂量 NAC 和 50 mg/kg/i.p/单次剂量 CsA。研究了肝组织样本的光镜和电镜改变。分析了血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）和肝谷胱甘肽（GSH）水平。评估了肝组织中 3-硝基酪氨酸和细胞色素 c 的免疫反应性。结果发现，APAP 导致小鼠肝脏的组织病理学和超微结构改变。此外，APAP 增加了细胞色素 c 和 3-硝基酪氨酸的免疫阳性染色。此外，APAP 组检测到肝 GSH 显著减少，血清 AST 和 ALT 水平升高。有趣的是，NAC+CsA 治疗改善了由 APAP 引起的组织学改变、细胞色素 c 和 3-硝基酪氨酸免疫反应性以及肝 GSH、血清 AST/ALT 水平。我们认为 NAC 和 CsA 的联合使用可减轻小鼠的对乙酰氨基酚诱导的肝毒性。
