Cadmium-induced Oxidative Stress and Immunosuppression Mediated Mitochondrial Apoptosis via JNK-FoxO3a-PUMA pathway in Common Carp (Cyprinus carpio L.) Gills

• Published in: Aquatic toxicology 2021-04, Vol.233, p.105775, Article 105775
• Main Authors: Chen, Jianqing, Chen, Dechun, Li, Jingxin, Liu, Yuanlong, Gu, Xianhong, Teng, Xiaohua
• Format: Article
• Language: English
• Subjects: Animals; Apoptosic injury; Apoptosis - drug effects; Apoptosis Regulatory Proteins - metabolism; Cadmium - toxicity; Carps - metabolism; Forkhead Transcription Factors - metabolism; Gills - drug effects; Gills - immunology; Gills - metabolism; Hydrogen Peroxide - metabolism; Immune Tolerance - drug effects; JNK-FoxO3a-PUMA pathway; MAP Kinase Signaling System - drug effects; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - pathology; Mitochondrion; Oxidation/antioxidation imbalance; Oxidative Stress - drug effects; Oxidative Stress - immunology; Random Allocation; Th17/Treg imbalance; Water Pollutants, Chemical - toxicity
• ISSN: 0166-445X; 1879-1514
• DOI: 10.1016/j.aquatox.2021.105775

•Cd exposure caused apoptosis via JNK-FoxO3a-PUMA and mitochondrial pathways.•Cd-caused apoptosis damage decreased the concentrations of essential elements.•Cd treatment caused oxidative stress via the imbalance of oxidation/antioxidation.•Excess Cd resulted in immunosuppression via the imbalance of Th17/Treg cells.•Oxidative stress and immunosuppression mediated Cd-induced apoptosis. Cadmium (Cd)-caused water environment pollution has become a matter of concern. Gill is an organ with respiratory and mucosal immune functions, and is also one of the organs directly attacked by pollutants. It was found that excess Cd could cause Cd accumulation and gill injury in carp. However, the mechanism of Cd-caused damage in common carp gills is still unclear. Oxidative stress, immunosuppression, and apoptosis took part in the mechanism of poisoning caused by some harmful substances. The aim of the study was to investigate complex molecular mechanism of apoptotic injury caused by Cd in common carp gills. Hence, in this study, we established a Cd poisoning model to explore whether excess Cd can induce apoptosis through observing histomorphology and apoptotic cells; and determining mineral elements, oxidative stress-related factors, immune-related, and apoptosis-related genes in common carp gills. Fifty-four fish were randomly separated into the control group and the Cd group and were cultured for 45 days. The water of the control group was drinking water and the water of the Cd group was CdCl2-added drinking water (0.26 mg/L Cd). In our results, we found that excess Cd increased Cd level, decreased the levels of essential mineral elements (Cu, Fe, Zn, and Mn), damaged mitochondria, and increased apoptotic cells in common carp gills, meaning that excess Cd caused Cd accumulation and apoptotic injury via mitochondrion in common carp gills. Furthermore, we found that Cd inhibited anti-apoptosis-related gene Bcl-2 and stimulated pro-apoptosis-related genes (JNK, FoxO3a, PUMA, Bax, Apaf-1, Caspase-9, and Caspase-3) on 15th, 30th, and 45th days. Above data meant that Cd exposure caused apoptosis via mitochondrion and JNK-FoxO3a-PUMA pathway in common carp gills. In addition, in our experiment, Cd treatment increased oxidants (H2O2 and MDA) and decreased antioxidants (CAT, GPx, GST, SOD, T-AOC, and GSH), indicating that Cd caused oxidative stress via oxidation/antioxidation imbalance. Meanwhile, compared to the control group, T-help 17 (Th17) cell-related factors (IL-17, TNF-α