Nephroprotective effect of gastrodin against lead-induced oxidative stress and inflammation in mice by the GSH, Trx, Nrf2 antioxidant system, and the HMGB1 pathway
Zhi-Kai Tian, Yujia Zhang, Feng Zhao-jun, Hong Jiang, Chao Cheng, Jian-Mei Sun, Chan‐Min Liu
Abstract
Abstract Gastrodin (GAS), the main phenolic glycoside derivative from Gastrodiaelata Blume, has several bio-activities. However, the molecular mechanisms of these protective actions currently remain unclear. This study aimed to investigate the mechanisms of GAS on lead (Pb)-induced oxidative stress and inflammation in the kidneys and primary kidney mesangial cells. Results indicated that GAS improved Pb-induced renal dysfunction and morphological changes in mice. GAS ameliorated Pb-induced inflammation in kidneys by reducing the TNF-α and IL-6 levels. GAS inhibited Pb-induced oxidative stress by regulating the glutathione, thioredoxin (Trx), and Nrf2 antioxidant systems. Furthermore, GAS supplementation increased the activation of SOD, GPx, HO-1, and NQO1 in the kidneys. GAS decreased the expression levels of HMGB1, TLR4, RAGE, MyD88, and NF-κB. These results were further confirmed in primary kidney mesangial cells. Collectively, this study demonstrated that GAS alleviated Pb-induced kidney oxidative stress and inflammation by regulating the antioxidant systems and the Nrf2 signaling pathway. Highlights Gastrodin ameliorated Pb-induced kidney injury in mice. Gastrodin inhibited oxidative stress and inflammation in kidneys. Gastrodin activated the GSH, Trx and Nrf2 antioxidant system in kidneys. Gastrodin inhibited the activities of HMGB1. RAGE, TLR4, and MyD88