Taurine alleviates kidney injury in a thioacetamide rat model by mediating Nrf2/HO-1, NQO-1, and MAPK/NF-κB signaling pathways
Amal M. H. Ghanim, Mahmoud R.T. Farag, Mahitab A. Anwar, Nada Ali, Mohammed A. Hawas, Hend M.E. Elsallab, Walaa A. Elhendawy, Lina A. Basyouni, Ola A. Refaey, Khaled E. Zaki, Noha A.M. Ali, Heba A. Metwaly
Abstract
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 (ERK) 1/2, nuclear factor kappa B (NF-κB), and tumor necrosis factor α (TNF-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.