Abstract
Abstract in English, Chinese The large yellow croaker (Larimichthys crocea), which is an economically important mariculture fish in China, is often exposed to environmental hypoxia. Reactive oxygen species (ROS) homeostasis is essential for the maintenance of normal physiological conditions in an organism. Direct evidence that environmental hypoxia leads to ROS overproduction is scarce in marine fish. Furthermore, the sources of ROS overproduction in marine fish under hypoxic stress are poorly known. In this study, we investigated the effects of hypoxia on redox homeostasis in L. crocea and the impact of impaired redox homeostasis on fish. We first confirmed that hypoxia drove ROS production mainly via the mitochondrial electron transport chain and NADPH oxidase complex pathways in L. crocea and its cell line (large yellow croaker fry (LYCF) cells). We subsequently detected a marked increase in the antioxidant systems of the fish. However, imbalance between the pro-oxidation and antioxidation systems ultimately led to excessive ROS and oxidative stress. Cell viability showed a remarkable decrease while oxidative indicators, such as malondialdehyde, protein carbonylation, and 8-hydroxy-2 deoxyguanosine, showed a significant increase after hypoxia, accompanied by tissue damage. N-acetylcysteine (NAC) reduced ROS levels, alleviated oxidative damage, and improved cell viability in vitro. Appropriate uptake of ROS scavengers (e.g., NAC and elamipretide Szeto-Schiller-31) and inhibitors (e.g., apocynin, diphenylene iodonium, and 5-hydroxydecanoate) may be effective at overcoming hypoxic toxicity. Our findings highlight previously unstudied strategies of hypoxic toxicity resistance in marine fish. 大黄鱼（Larimichthys crocea）是我国重要的海水养殖经济鱼类。其主要养殖方式为近海网箱养殖，养殖海区低氧已成为影响大黄鱼养殖产业健康可持续发展的不利因素之一。活性氧（ROS）稳态（又称氧化还原稳态）对于维持生物体的正常生理状态至关重要。目前，在海洋鱼类中，环境低氧导致ROS过量产生的直接证据较少。此外，低氧胁迫下海洋鱼类中过量产生的ROS的来源也尚不清楚。该研究探究了低氧胁迫对大黄鱼氧化还原稳态的影响以及氧化还原稳态失衡对鱼类的影响。研究结果显示，低氧胁迫主要通过线粒体电子运输链（ETC）和NADPH氧化酶复合体（NOX）途径驱动大黄鱼及大黄鱼仔鱼细胞系（LYCF细胞）中ROS的产生；低氧胁迫下大黄鱼抗氧化防御系统被激活但未能及时清除过量的ROS，过量ROS进一步诱发氧化应激指标如丙二醛（MDA）、蛋白质羰基化（PCO）和8-羟基-2脱氧鸟苷（8-OHdG）等的上升及细胞活力的下降，并伴随着鱼体组织结构的损伤；N-乙酰半胱氨酸（NAC）降低了低氧胁迫下LYCF细胞中的ROS水平，减轻了氧化损伤，并提高了细胞活力。ROS清除剂（如NAC和埃拉米肽SS-31）和抑制剂（如香草酮（Apocynin）、二苯基碘（DPI）及5-羟基葵酸盐（5-HD））可能能有效减轻低氧胁迫对大黄鱼的氧化毒性（Oxidative toxicity）。该研究可为阐释鱼类低氧应答机理积累基础生物学资料，同时为今后大黄鱼养殖生产中提高其低氧耐受性提供参考。.