Oyouni Atif Abdulwahab A, Saggu Shalini, Tousson Ehab, Rehman Hasibur
Department of Biology, Faculty of Sciences, University of Tabuk, Tabuk, 71491, Saudi Arabia.
Department of Zoology, Faculty of Sciences, Tanta University, Tanta, 31527, Egypt.
Toxicol Rep. 2018 Jun 2;5:687-694. doi: 10.1016/j.toxrep.2018.06.003. eCollection 2018.
Tacrolimus (TAC) is used sporadically as an immunosuppressive agent for organ transplantation, but its clinical used is limited due to its marked nephrotoxicity. L. (Lamiaceae) (OB) had been shown to possess antioxidant, anti-inflammatory and nephroprotective activity, and effective at improving renal inflammation and glomerular. In our study, we aim to evaluate the efficacy of the OB against TAC-induced mitochondrial nephrotoxicity in CD1 mice. Mice were randomly divided into four groups. Group 1 (control group); administered orally with normal saline (1 mL/kg) for two weeks; Group 2 (OB extract treated-group) (500 mg/kg b.wt) gavaged once/day for two weeks; Group 3 (TAC-treated group) (3 mg/kg b.wt, administered ip once a day for two weeks); and Group 4; (TAC plus OB extract treated-group). Tacrolimus-induced nephrotoxicity was assessed biochemically and histopathologically. The OB extract was high in phenolic content (50.3 mg/g of gallic acid equivalent), total flavonoids (14.5 mg/g CE equivalent). The potential antioxidant efficacy of the extract (IC) was 24.5 μg/mL. OB pretreatment significantly improved the TAC-induced changes in biochemical markers of nephrotoxicity for instance blood urea nitrogen (BUN), creatinine, total protein, and albumin (P < 0.01, when compared with TAC treated group). Also, it significantly restored the increase activities of TBARS, protein carbonyl (PC) (P < 0.001, when compared to healthy control group) and decreased activities of nonprotein thiol (NP-SH) levels, Mn-superoxide dismutase (Mn-SOD) and glutathione peroxidase (GPx) antioxidants of mitochondria. The nephroprotective efficacy of the OB leaves extract was further evident by histopathological analysis together with the PCNA-ir and Bcl2. The upshot of the present study revealed that the OB possessed significant antioxidant and nephroprotective activity and had a preventive effect on the biochemical alterations and histological changes in TAC-treated mice.
他克莫司（TAC）偶尔用作器官移植的免疫抑制剂，但其临床应用因明显的肾毒性而受到限制。唇形科植物（OB）已被证明具有抗氧化、抗炎和肾保护活性，并且在改善肾脏炎症和肾小球方面有效。在我们的研究中，我们旨在评估OB对CD1小鼠中TAC诱导的线粒体肾毒性的疗效。小鼠被随机分为四组。第1组（对照组）；口服生理盐水（1 mL/kg）两周；第2组（OB提取物治疗组）（500 mg/kg体重）每天灌胃一次，持续两周；第3组（TAC治疗组）（3 mg/kg体重，每天腹腔注射一次，持续两周）；第4组；（TAC加OB提取物治疗组）。通过生化和组织病理学评估他克莫司诱导的肾毒性。OB提取物的酚类含量高（50.3 mg/g没食子酸当量），总黄酮含量高（14.5 mg/g CE当量）。提取物的潜在抗氧化功效（IC）为24.5 μg/mL。OB预处理显著改善了TAC诱导的肾毒性生化标志物变化，例如血尿素氮（BUN）、肌酐、总蛋白和白蛋白（与TAC治疗组相比，P < 0.01）。此外，它显著恢复了丙二醛（TBARS）、蛋白质羰基（PC）的增加活性（与健康对照组相比，P < 0.001），并降低了线粒体非蛋白硫醇（NP-SH）水平、锰超氧化物歧化酶（Mn-SOD）和谷胱甘肽过氧化物酶（GPx）抗氧化剂的活性。通过组织病理学分析以及增殖细胞核抗原免疫反应（PCNA-ir）和Bcl2进一步证明了OB叶提取物的肾保护功效。本研究结果表明，OB具有显著的抗氧化和肾保护活性，对TAC治疗的小鼠的生化改变和组织学变化具有预防作用。
