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Updated: Sep 25, 2025
Studying Neurobehavioral Effects of Environmental Pollutants on Zebrafish Larvae
Published on: February 5, 2020
Chlorine disinfection byproduct of diazepam affects nervous system function and possesses gender-related difference
Xiaole Zhao1, Xiaoyong Huang2, Wenjing Peng3
1College of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, People's Republic of China; Institute of Food Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, People's Republic of China.
Abstract:
Chlorinated disinfection byproducts in water posed potential health threat to humans. Nowadays, chlorinated derivatives of diazepam were ubiquitously detected in drinking water. Among these derivatives, 2-methylamino-5-chlorobenzophenone (MACB) was capable of penetrating the blood-brain barrier (BBB) and induced microglial phagocytosis of neurons in zebrafish. However, little is known about the MACB metabolism in vivo. Here, we determined the metabolism of MACB in zebrafish and microglia cell model. We found that MACB mainly disrupted the metabolism of branched-chain amino acids (Leu, Ile and Val) in zebrafish model and gamma-aminobutyric acid (GABA) pathway-related amino acids in microglia model. Additionally, we demonstrated that MACB can be metabolized by the mixed-function oxidase CYP1A2 enzyme which could be inhibited by estrogen causing the gender-difference in the accumulation of MACB in vivo. These results indicated that MACB perturbed metabolism and induced neurological disorders, particularly in the female zebrafish.
