Climbazole causes cell apoptosis and lipidosis in the liver of grass carp

Zhi-Jie Lu; Wen-Jun Shi; Fang-Zhou Gao; Dong-Dong Ma; Jin-Ge Zhang; Si-Ying Li; Xiao-Bing Long; Qian-Qian Zhang; Guang-Guo Ying

doi:10.1016/j.aquatox.2023.106698

Climbazole causes cell apoptosis and lipidosis in the liver of grass carp

Aquat Toxicol. 2023 Oct:263:106698. doi: 10.1016/j.aquatox.2023.106698. Epub 2023 Sep 15.

Authors

Zhi-Jie Lu¹, Wen-Jun Shi², Fang-Zhou Gao¹, Dong-Dong Ma¹, Jin-Ge Zhang¹, Si-Ying Li¹, Xiao-Bing Long¹, Qian-Qian Zhang¹, Guang-Guo Ying¹

Affiliations

¹ SCNU Environmental Research Institute, Guangdong Provincial Key Laboratory of Chemical Pollution and Environmental Safety & MOE Key Laboratory of Theoretical Chemistry of Environment, South China Normal University, Guangzhou 510006, China; School of Environment, South China Normal University, University Town, Guangzhou 510006, China.
² SCNU Environmental Research Institute, Guangdong Provincial Key Laboratory of Chemical Pollution and Environmental Safety & MOE Key Laboratory of Theoretical Chemistry of Environment, South China Normal University, Guangzhou 510006, China; School of Environment, South China Normal University, University Town, Guangzhou 510006, China. Electronic address: wenjun.shi@m.scnu.edu.cn.

PMID: 37722153
DOI: 10.1016/j.aquatox.2023.106698

Abstract

Climbazole, an azole, is widely used in personal care products, pharmaceuticals, and pesticides and is frequently detected in surface water. Climbazole has showed endocrine-disrupting effects. However, the effects of climbazole in fish are still largely unclear. In this study, grass carp (Ctenopharyngodon idella) and liver cell lines (L8824 cells) were treated with climbazole at concentrations ranging from 0.2 to 20 μg/L for 42 days in vivo and 24 h in vitro to evaluate the effects on the liver, respectively. Pathological, biochemical, and gene transcription and expression analyses were conducted to examine the hepatotoxicity. Our results showed that climbazole significantly decreased the hepatosomatic index, caused cell apoptosis in vivo and in vitro, and finally accumulated lipids in the liver. Beside, climbazole increased ROS levels, reduced Nrf2 and Keap1 mRNA and protein levels, and further decreased transcription of Nrf2-dependent downstream antioxidant enzyme genes, causing oxidative stress. Moreover, climbazole increased transcription and protein levels of apoptosis-related genes. Finally, climbazole damaged mitochondrial function and structure, disrupted liver lipid metabolism. Overall, climbazole caused hepatotoxicity, leading to a high ecological risk for aquatic organisms.

Keywords: Apoptosis; Climbazole; Grass carp; Hepatic lipidosis; Oxidative stress.