Investigation of dichlorodiphenyltrichloroethane (DDT) on xenobiotic enzyme disruption and metabolomic bile acid biosynthesis in DDT-sprayed areas using wild rats

Dichlorodiphenyltrichloroethane (DDT) is an organochlorine insecticide used worldwide. Several studies have reported the toxic effects of DDT and its metabolites on steroid hormone biosynthesis; however, its environmental effects are not well understood. This study examined wild rats collected in DDT-sprayed areas of South Africa and quantified plasma metabolites using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS). Fold change analysis of the metabolome revealed the effect of DDT on bile acid biosynthesis. Gene expression of the related enzyme in rat liver samples was also quantified. Significant association was found between DDT and gene expression levels related to constitutive androstane receptor mediated enzymes, such as Cyp2b1 in rat livers. However, our results could not fully demonstrate that enzymes related to bile acid biosynthesis were strongly affected by DDT. The correlation between DDT concentration and gene expression involved in steroid hormone synthesis in testis was also evaluated; however, no significant correlation was found. The disturbance of metabolic enzymes occurred in rat liver in the target area. Our results suggest that DDT exposure affects gene expression in wild rats living in DDT-sprayed areas. Therefore, there is a need for DDT toxicity evaluation in mammals living in DDT-sprayed areas. We could not find an effective biomarker that could reflect the mechanism of DDT exposure; however, this approach can provide new insights for future research to evaluate DDT effects in sprayed areas.