3,6-Dichlorocarbazole induces metabolic disturbances and activates drug detoxification processes in the liver of zebrafish (Danio rerio).

Polyhalogenated carbazoles (PHCZs) are widely recognized for their persistence and widespread presence in aquatic environments. Although PHCZ accumulation in aquatic organisms induces various forms of biological toxicity, the effects on liver metabolism are not yet fully understood. This study investigated the biological concentration factor (BCF), liver histopathology, metabolomics, and responses of key metabolic genes in the liver tissues of male zebrafish exposed to 20 and 100 μg/L of 3,6-dichlorocarbazole (3,6-DCCZ) for 21 days. The bioconcentration factor of 3,6-DCCZ was found to reach 109.7, based on measurements of both the exposure concentration in water and its concentration in liver tissue. Histopathological observations revealed that 3,6-DCCZ induced liver damage, including hepatic inflammatory infiltration, hepatocyte swelling, and disorganized hepatic cord arrangement. Metabolomics and metabolic gene analyses found that 3,6-DCCZ significantly reduced intermediates in glycolysis and the tricarboxylic acid cycle, potentially hindering liver glycolysis and glycogen synthesis. Additionally, 3,6-DCCZ increased the accumulation of triglycerides and fatty acids in zebrafish, potentially leading to liver lipid metabolism disorders. The increased expression of the alt gene further confirms liver damage. Furthermore, the expression of phase I and II detoxification genes (cyp1a, cyp3a65, ugt1ab, and ugt2a1) was dramatically upregulated, promoting the hepatic drug detoxification process. Overall, this study emphasizes that exposure to 3,6-DCCZ induces metabolic disorders and liver damage in zebrafish, providing a basis for understanding its potential ecological and health risks.