Pentachlorophenol exposure induced neurotoxicity by disrupting citrulline metabolism in larvae and adult zebrafish

• Published in: Toxicology and applied pharmacology Vol. 478; p. 116708
• Main Authors: Zhang, Yi, Li, Wenzheng, Zhu, Jun, Qian, Xin, Pei, Wenlong, Gu, Zhenyang, Wu, Qian, Zhang, Zhan, Li, Lei
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.11.2023
• Subjects: Citrulline; Locomotor activity; Neurotoxicity; Pentachlorophenol; Zebrafish; Zebrafish; Neurotoxicity; Pentachlorophenol; Citrulline; Locomotor activity
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2023.116708

Pentachlorophenol (PCP) is a ubiquitous environmental toxicant with various adverse effects. Although its neurotoxicity has been reported, the underlying mechanism and subsequent detoxification remain unclear. In this study, embryos and adult zebrafish were exposed to PCP to determine its potential neurotoxic mechanism and protective indicators. The survival rate, heart rate, mobility time, active status and moving distance were significantly decreased in larvae after 30 μg/L PCP exposure. Likewise, the mobile time, latency to the first movement, velocity and moving distance of adult zebrafish were significantly reduced by PCP exposure. Untargeted metabolomics analysis of larvae revealed that arginine and proline metabolism was the primary pathway affected by PCP exposure, reflected by increased proline and decreased citrulline (CIT) contents, which were confirmed by quantitative data. PCP exposure suppressed the conversion from arginine to CIT in larvae by downregulating the expression of nos1 and nos2a. Ornithine content was increased in the brains and intestines of adult zebrafish after PCP exposure, which inhibited ornithine catabolism to CIT by downregulating otc, resulting in reduced CIT. Intriguingly, CIT supplementation significantly restored the neurobehavioral defects induced by PCP in larvae and adult zebrafish. CIT supplementation upregulated the expression of ef1α and tuba1 in larvae and inhibited the downregulation of ef1α in the brains of adult zebrafish. Taken together, these results indicated that CIT supplementation could protect against PCP-induced neurotoxicity by upregulating the expression of genes involved in neuronal development and function. •PCP exposure inhibited locomotor activity of zebrafish larvae and adult zebrafish.•PCP exposure disrupt arginine and proline metabolism of zebrafish larvae.•Citrulline supplementation restored the impaired locomotor activity induced by PCP.•Citrulline supplementation upregulated neurodevelopment-related genes.