Effects of chlorothalonil, prochloraz and the combination on intestinal barrier function and glucolipid metabolism in the liver of mice.

Chlorothalonil (CHL) and procymidone (PRO) are fungicides that exhibit low toxicity and are widely used in many countries. And both fungicides are frequently detected in the food chain. However, the health risk posed by these fungicides is still unclear. Here, 8-week-old male C57BL/6 mice were orally treated with CHL (10, 50 mg/kg/day), PRO (20, 100 mg/kg/day) and CHL+PRO (5+10, 25+50 mg/kg/day) by dietary supplementation for 10 weeks. Hepatic pathological analysis showed that exposure to CHL, PRO and CHL+PRO could cause liver injury. The glucose, triglyceride (TG) levels and the related gene expression to glucolipid metabolism changed significantly. The significantly reduced acylcarnitine levels demonstrated that CHL, PRO and CHL+PRO exposure inhibited fatty acids (FAs) β-oxidation. In addition, CHL and PRO altered the structure of the gut microbiota and destroyed the integrity of the intestinal barrier function. In particular, AF12, Odoribacter, Prevotella and Lactobacillus were highly correlated with carnitine. The results showed that CHL, PRO and CHL+PRO exposure might inhibit FAs β-oxidation by decreasing cystic fibrosis transmembrane conductance regulator (CFTR)-mediated ion transport, indicating that these fungicides disturbed intestinal barrier function associated with glucolipid metabolism disorder. Here, the data also indicated that there was an additive effect between CHL and PRO in mice.