Effects of triadimefon on the metabolism of cultured hepatocytes

Vidya V. Iyer, Ioannis P. Androulakis, Charles M. Roth, Marianthi G. Ierapetritou

Research output: Chapter in Book/Report/Conference proceedingConference contribution

1 Scopus citations

Abstract

The liver, being the major site of metabolism, plays a critical role in xenobiotic biotransformation and clearance. Quantifying the links between central hepatic and xenobiotic metabolism is critical to understanding toxicant-induced hepatic injury. Conazoles are a class of azole fungicides used to prevent fungal growth in fruits, vegetables and seeds, and for the treatment of fungal infections. Certain conazoles (such as triadimefon) are found to be tumorigenic in rats and mice. In this study, cultured primary rat hepatocytes were treated to varying doses (< 0.3 mM) of triadimefon on a temporal basis with daily media change. Following exposure, supernatant was collected daily for 3 days and concentration of various metabolites (triadimefon, glucose, urea, albumin, amino acids, fatty acids, cholesterol etc.) in the media and supernatant were quantified. Albumin production was reduced in 0.3 mM triadimefon treated cells by the end of three days whereas urea production was not significantly affected. Metabolic network flexibility analysis (MNFA) demonstrated that by the end of the three day period, 0.3 mM triadimefon treated cells exhibited a major switch in hepatic metabolism by producing glucose, instead of glucose consumption. We also observed fatty acid oxidation instead of fatty acid synthesis in 0.3 mM triadimefon treated cells. Fatty acid oxidation also caused higher flux through the TCA cycle which in turn drove gluconeogenesis in these cells. It is likely that fatty acid oxidation is active in order to supply energy that is required by the phase I oxidation of triadimefon detoxification.

Original languageEnglish (US)
Title of host publication10th IEEE International Conference on Bioinformatics and Bioengineering 2010, BIBE 2010
Pages118-123
Number of pages6
DOIs
StatePublished - 2010
Event10th IEEE International Conference on Bioinformatics and Bioengineering, BIBE-2010 - Philadelphia, PA, United States
Duration: May 31 2010Jun 3 2010

Publication series

Name10th IEEE International Conference on Bioinformatics and Bioengineering 2010, BIBE 2010

Other

Other10th IEEE International Conference on Bioinformatics and Bioengineering, BIBE-2010
Country/TerritoryUnited States
CityPhiladelphia, PA
Period5/31/106/3/10

All Science Journal Classification (ASJC) codes

  • Biomedical Engineering
  • Health Informatics

Keywords

  • Energy metabolism
  • Fatty acid oxidation
  • Glycolysis or gluconeogenesis
  • Metabolic network flexibility analysis
  • Triadimefon detoxification

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