Hui Yang , Kang Ou-Yang , Ya He , Xinyu Wang , Liangmou Wang , Qing Yang , Dapeng Li , Li Li
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引用次数: 0
Abstract
Nitrite, a highly toxic environmental contaminant, induces various physiological toxicities in aquatic animals. Herein, we investigate the in vivo effects of nitrite exposure at concentrations of 0, 0.2, 2, and 20 mg/L on glucose and lipid metabolism in zebrafish. Our results showed that exposure to nitrite induced mitochondrial oxidative stress in zebrafish liver and ZFL cells, which were evidenced by increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) as well as decreased mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP). Changes in these oxidative stress markers were accompanied by alterations in the expression levels of genes involved in HIF-1α pathway (hif1α and phd), which subsequently led to the upregulation of glycolysis and gluconeogenesis-related genes (gk, pklr, pdk1, pepck, g6pca, ppp1r3cb, pgm1, gys1 and gys2), resulting in disrupted glucose metabolism. Moreover, nitrite exposure activated ERs (Endoplasmic Reticulum stress) responses through upregulating of genes (atf6, ern1 and xbp1s), leading to increased expression of lipolysis genes (pparα, cpt1aa and atgl) and decreased expression of lipid synthesis genes (srebf1, srebf2, fasn, acaca, scd, hmgcra and hmgcs1). These results were also in consistent with the observed changes in glycogen, lactate and decreased total triglyceride (TG) and total cholesterol (TC) in the liver of zebrafish. Our in vitro results showed that co-treatment with Mito-TEMPO and nitrite attenuated nitrite-induced oxidative stress and improved mitochondrial function, which were indicated by the restorations of ROS, MMP, ATP production, and glucose-related gene expression recovered. Co-treatment of TUDCA and nitrite prevented nitrite-induced ERs response and which was proved by the levels of TG and TC ameliorated as well as the expression levels of lipid metabolism-related genes. In conclusion, our study suggested that nitrite exposure disrupted hepatic glucose and lipid metabolism through mitochondrial dysfunction and ERs responses. These findings contribute to the understanding of the potential hepatotoxicity for aquatic animals in the presence of ambient nitrite.
期刊介绍:
Aquatic Toxicology publishes significant contributions that increase the understanding of the impact of harmful substances (including natural and synthetic chemicals) on aquatic organisms and ecosystems.
Aquatic Toxicology considers both laboratory and field studies with a focus on marine/ freshwater environments. We strive to attract high quality original scientific papers, critical reviews and expert opinion papers in the following areas: Effects of harmful substances on molecular, cellular, sub-organismal, organismal, population, community, and ecosystem level; Toxic Mechanisms; Genetic disturbances, transgenerational effects, behavioral and adaptive responses; Impacts of harmful substances on structure, function of and services provided by aquatic ecosystems; Mixture toxicity assessment; Statistical approaches to predict exposure to and hazards of contaminants
The journal also considers manuscripts in other areas, such as the development of innovative concepts, approaches, and methodologies, which promote the wider application of toxicological datasets to the protection of aquatic environments and inform ecological risk assessments and decision making by relevant authorities.