Prostaglandin Metabolome Profiles in Zebrafish (Danio rerio) Exposed to Acetochlor and Butachlor

Abstract

Prostaglandins (PGs) are critically important signaling molecules that play key roles in normal and pathophysiological processes. Many endocrine-disrupting chemicals have been found to suppress PG synthesis; however, studies about the effects of pesticides on PGs are limited. The effects of two known endocrine disrupting herbicides, acetochlor (AC) and butachlor (BC), on PG metabolites in zebrafish (Danio rerio) females and males were studied using widely targeted metabolomics analysis based on ultraperformance liquid chromatography—tandem mass spectrometry (UPLC—MS/MS). In total, 40 PG metabolites were detected in 24 zebrafish samples, including female and male samples, with and without exposure to AC or BC at the sub-lethal concentration of 100 μg/L for 96 h. Among them, 19 PGs significantly responded to AC or BC treatment, including 18 PGs that were upregulated. The enzyme-linked immunosorbent assay (ELISA) test in zebrafish showed BC could cause significant upregulation of an isoprostane metabolite, 5-iPF2a-VI, which is positively related to the elevated level of reactive oxygen species (ROS). The present study guides us to conduct a further study to determine whether PG metabolites, including isoprostanes, could be potential biomarkers for chloracetamide herbicides.

Metabolomics in Preclinical Drug Safety Assessment: Current Status and Future Trends

“…Metabolomics is a powerful tool used to investigate the responses of metabolite profiles in organisms exposed to various substances. For instance, a study applied metabolomics to investigate the responses of metabolite profiles in zebrafish exposed to acetochlor and butachlor, two substances that could disrupt the thyroid and sex steroid endocrine systems in zebrafish [7]. Metabolomics can give insights into toxicity pathways and mechanisms, e.g., metabolomics is an emerging approach used to identify and discover metabolic biomarkers, providing a series of metabolic signatures that elucidate the pathological changes in diseases, including Parkinson's disease [8].…”