Chronic exposure to fungicide propamocarb induces bile acid metabolic disorder and increases trimethylamine in C57BL/6J mice.

Abstract

Propamocarb (PM) is a widely used fungicide that affects lipid biosynthesis in fungi. In this study, we explored the effects of PM on mouse metabolism and gut microbiota-related pathways by exposing C57BL/6J mice to 1, 3, and 10 mg/L PM through drinking water for a duration of 10 weeks. We found that hepatic bile acids (BAs) were considerably increased in the PM-treated group. The transcription of genes related to BA synthesis and transportation were also markedly altered in the liver and the ileum; accordingly, serous BA profiles were changed. BAs are tightly associated with energy metabolism and the gut microbiota; as expected, we observed that hepatic glycolysis; β-oxidation; fatty acid transportation, release and synthesis; and triacylglycerol synthesis and transportation were significantly altered at the transcriptional level. Gut microbial community structures were significantly changed both in cecal contents and feces. Using Linear discriminant analysis Effect Size (LEfSe), we found that Chloroflexi, Bacteroidetes and Actinobacteria phyla; Prevotellaceae, Odoribacteraceae and Porphyromonadaceae families; and Butyricimonas, Oscillospira, Parabacteroides, Prevotella and Dorea genera enriched in PM-treated mice. Fecal metabolites involved in energy metabolism were likewise altered. In addition, the atherosclerosis-promoting molecule trimethylamine was significantly increased in feces, which induced a disturbance in the cardiac NO/NOS pathway and an increase in NF-κB transcriptional levels. Our findings indicated that chronic PM exposure induced disorders in enterohepatic metabolism and had potential to increase the risk of cardiovascular disease.

• Authors: Sisheng Wu, Ting Luo, Siyu Wang, Jicong Zhou, Yingchun Ni, Zhengwei Fu, Yuanxiang Jin
• Journal: The Science of the total environment (Sci Total Environ) Vol. 642 Pg. 341-348 (Nov 15 2018) ISSN: 1879-1026 [Electronic] Netherlands
• PMID: 29906725 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Bile Acids and Salts
• Carbamates
• Methylamines
• propamocarb
• trimethylamine

Topics

• Animals
• Bile Acids and Salts (metabolism)
• Carbamates (toxicity)
• Liver
• Metabolic Diseases (chemically induced)
• Methylamines (metabolism)
• Mice
• Mice, Inbred C57BL
• Toxicity Tests