Ghanim Amal M H, Farag Mahmoud R T, Anwar Mahitab A, Ali Nada A M, Hawas Mohammed A, Elsallab Hend M E, Elhendawy Walaa A, Basyouni Lina A, Refaey Ola A, Zaki Khaled E, Ali Noha A M, Metwaly Heba A
Department of Biochemistry, Faculty of Pharmacy, Fayoum University, Fayoum 63514, Egypt.
Department of Pharmacology, Faculty of Pharmacy, Delta University, Gamasa 35712, Egypt.
Can J Physiol Pharmacol. 2022 Apr;100(4):352-360. doi: 10.1139/cjpp-2021-0488. Epub 2021 Oct 25.
This study investigated the molecular mechanisms by which taurine exerts its reno-protective effects in thioacetamide (TAA) - induced kidney injury in rats. Rats received taurine (100 mg/kg daily, intraperitoneally) either from day 1 of TAA injection (250 mg/kg twice weekly for 6 weeks) or after 6 weeks of TAA administration. Taurine treatment, either concomitant or later as a therapy, restored kidney functions, reduced blood urea nitrogen (BUN), creatinine, and malondialdehyde (MDA), increased renal levels of superoxide dismutase (SOD), and reversed the increase of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) caused by TAA. Taurine treatment also led to a significant rise in nuclear factor erythroid 2-related factor 2 (Nrf2), hemoxygenase-1 (HO-1), and NADPH quinone oxidoreductase-1 (NQO-1) levels, with significant suppression of extracellular signal-regulated kinase () 1/2, nuclear factor kappa B (), and tumor necrosis factor α () gene expressions, and interleukin-18 (IL-18) and TNF-α protein levels compared with those in TAA kidney-injured rats. Taurine exhibited reno-protective potential in TAA-induced kidney injury through its antioxidant and anti-inflammatory effects. Taurine antioxidant activity is accredited for its effect on Nrf-2 induction and subsequent activation of HO-1 and NQO-1. In addition, taurine exerts its anti-inflammatory effect via regulating NF-κB transcription and subsequent production of pro-inflammatory mediators via mitogen-activated protein kinase (MAPK) signaling regulation.
本研究探讨了牛磺酸在硫代乙酰胺（TAA）诱导的大鼠肾损伤中发挥肾保护作用的分子机制。大鼠从TAA注射第1天起（每周两次，每次250mg/kg，共6周）或在TAA给药6周后接受牛磺酸（每日100mg/kg，腹腔注射）。牛磺酸治疗，无论是同时进行还是稍后作为一种疗法，均可恢复肾功能，降低血尿素氮（BUN）、肌酐和丙二醛（MDA）水平，提高肾脏超氧化物歧化酶（SOD）水平，并逆转TAA所致的肾损伤分子-1（KIM-1）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）的升高。牛磺酸治疗还导致核因子红细胞2相关因子2（Nrf2）、血红素加氧酶-1（HO-1）和NADPH醌氧化还原酶-1（NQO-1）水平显著升高，与TAA肾损伤大鼠相比，细胞外信号调节激酶（）1/2、核因子κB（）和肿瘤坏死因子α（）基因表达以及白细胞介素-18（IL-18）和TNF-α蛋白水平受到显著抑制。牛磺酸通过其抗氧化和抗炎作用在TAA诱导的肾损伤中表现出肾保护潜力。牛磺酸的抗氧化活性归因于其对Nrf-2的诱导作用以及随后对HO-1和NQO-1的激活。此外，牛磺酸通过调节NF-κB转录以及随后通过丝裂原活化蛋白激酶（MAPK）信号调节产生促炎介质来发挥其抗炎作用。
