Moustafa Ahmed H, Pasha Heba F, Abas Manar A, Aboregela Adel M
Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, Egypt.
Department of Medical Biochemistry and Genetics, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Anat Cell Biol. 2023 Mar 31;56(1):109-121. doi: 10.5115/acb.22.200. Epub 2022 Dec 22.
Thioacetamide (TAA) exposure and hepatitis C virus infection are usually associated with renal dysfunction. Sofosbuvir (SFV) and daclatasvir (DAC) drugs combination has great value in the treatment of hepatitis C. The study aimed to identify the nephrotoxic effects of TAA and to evaluate the ameliorative role of SFV and DAC in this condition. Forty-eight adult male albino rats were divided into eight groups and received saline (control), SFV, DAC, SFV+DAC, TAA, TAA+SFV, TAA+DAC and TAA+SFV+DAC for eight weeks. Kidney and blood samples were retrieved and processed for histological (Hematoxylin and Eosin and Masson's trichrome), immunohistochemical (α-smooth muscle actin), and biochemical analysis (urea, creatinine, total protein, albumin, malondialdehyde, reduced glutathione, superoxide dismutase, and tumor necrosis factor-α). Examination revealed marked destruction of renal tubules on exposure to TAA with either hypertrophy or atrophy of glomeruli, increase in collagen deposition, and wide expression of α-smooth muscle actin. Also, significant disturbance in kidney functions, oxidative stress markers, and tumor necrosis factor-α. Supplementation with either SFV or DAC produced mild improvement in the tissue and laboratory markers. Moreover, the combination of both drugs greatly refined the pathology induced by TAA at the cellular and laboratory levels. However, there are still significant differences when compared to the control. In conclusion, SFV and DAC combination partially but greatly ameliorated the renal damage induced by TAA which might be enhanced with further supplementations to give new hope for those with nephropathy associated with hepatitis.
硫代乙酰胺（TAA）暴露和丙型肝炎病毒感染通常与肾功能障碍有关。索磷布韦（SFV）和达卡他韦（DAC）联合用药在丙型肝炎治疗中具有重要价值。本研究旨在确定TAA的肾毒性作用，并评估SFV和DAC在此情况下的改善作用。将48只成年雄性白化大鼠分为八组，分别给予生理盐水（对照组）、SFV、DAC、SFV+DAC、TAA、TAA+SFV、TAA+DAC和TAA+SFV+DAC，持续八周。采集肾脏和血液样本，进行组织学（苏木精和伊红染色以及Masson三色染色）、免疫组织化学（α-平滑肌肌动蛋白）和生化分析（尿素、肌酐、总蛋白、白蛋白、丙二醛、还原型谷胱甘肽、超氧化物歧化酶和肿瘤坏死因子-α）。检查发现，暴露于TAA后肾小管有明显破坏，伴有肾小球肥大或萎缩，胶原沉积增加，α-平滑肌肌动蛋白广泛表达。此外，肾功能、氧化应激标志物和肿瘤坏死因子-α也有明显紊乱。单独补充SFV或DAC可使组织和实验室指标有轻度改善。此外，两种药物联合使用在细胞和实验室水平上大大改善了TAA所致的病理变化。然而，与对照组相比仍有显著差异。总之，SFV和DAC联合用药部分但大大改善了TAA所致的肾损伤，进一步补充可能会增强这种作用，为丙型肝炎相关肾病患者带来新希望。
