Eucommia ulmoides Extract Attenuates Oxidative Stress, Endoplasmic Reticulum Stress and Apoptosis Induced by Acute Hypoxia via the Nrf2/Keap1 Pathway in Largemouth Bass (Micropterus salmoides)

Due to the hypoxic environment caused by global warming and intensive aquaculture process, fish are susceptible to oxidative damage and death. Eucommia ulmoides extract (EUE) has demonstrated antioxidant and anti-inflammatory properties. However, whether EUE can mitigate hypoxia-induced negative effects remains uninvestigated in fish. This study investigated the effect of 0 and 1.0 g/kg EUE on acute hypoxia-induced damage in largemouth bass and its potential mechanisms. The results showed that EUE alleviated the deterioration of plasma activities (ALT and AST) induced by acute hypoxic stress, decreased the number of macrophages and increased the total number of blood cells. EUE was effective in reducing the level of apoptosis and the content of ROS, Ca2+, and NO in blood cells. Additionally, EUE alleviated liver tissue injury caused by acute hypoxic stress, which could be associated with increased total antioxidant capacity and antioxidant enzyme activities (SOD, CAT and GSH-Px). Furthermore, EUE up-regulated the expression levels of Nrf2 and CAT, activated XBP1 and IRE expression and down-regulated GRP78 expression, relieving the endoplasmic reticulum (ER) stress response. The down-regulation of Caspase3 and Caspase9 is evidence that EUE inhibited apoptosis in acute hypoxic stress. In summary, EUE reduced oxidative damage, ER stress, and apoptosis caused by hypoxic stress via the Nrf2/Keap1 signaling pathway in largemouth bass. This study presents a part of the theoretical foundation for the EUE to resist damage caused by hypoxic stress, thereby establishing a basis for sustainable development in aquaculture.