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Phosphatidylcholine (18:0/20:4), a potential biomarker to predict ethionamide-induced hepatic steatosis in rats.

Abstract
Ethionamide (ETH), a second-line drug for multidrug-resistant tuberculosis, is known to cause hepatic steatosis in rats and humans. To investigate predictive biomarkers for ETH-induced steatosis, we performed lipidomics analysis using plasma and liver samples collected from rats treated orally with ETH at 30 and 100 mg/kg for 14 days. The ETH-treated rats developed hepatic steatosis with Oil Red O staining-positive vacuolation in the centrilobular hepatocytes accompanied by increased hepatic contents of triglycerides (TG) and decreased plasma TG and total cholesterol levels. A multivariate analysis for lipid profiles revealed differences in each of the 35 lipid species in the plasma and liver between the control and the ETH-treated rats. Of those lipids, phosphatidylcholine (PC) (18:0/20:4) decreased dose-dependently in both the plasma and liver. Moreover, serum TG-rich very low-density lipoprotein (VLDL) levels, especially the large particle fraction of VLDL composed of PC containing arachidonic acid (20:4) involved in hepatic secretion of TG, were decreased dose-dependently. In conclusion, the decreased PC (18:0/20:4) in the liver, possibly leading to suppression of hepatic TG secretion, was considered to be involved in the pathogenesis of the ETH-induced hepatic steatosis. Therefore, plasma PC (18:0/20:4) levels are proposed as mechanism-related biomarkers for ETH-induced hepatic steatosis.
AuthorsKyotaka Muta, Kosuke Saito, Yusuke Kemmochi, Taku Masuyama, Akio Kobayashi, Yoshiro Saito, Shoichiro Sugai
JournalJournal of applied toxicology : JAT (J Appl Toxicol) Vol. 42 Issue 9 Pg. 1533-1547 (09 2022) ISSN: 1099-1263 [Electronic] England
PMID35315511 (Publication Type: Journal Article)
Copyright© 2022 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd.
Chemical References
  • Biomarkers
  • Phosphatidylcholines
  • Triglycerides
  • Ethionamide
Topics
  • Animals
  • Biomarkers
  • Ethionamide (therapeutic use, toxicity)
  • Fatty Liver (chemically induced, drug therapy)
  • Humans
  • Liver (pathology)
  • Phosphatidylcholines
  • Rats
  • Triglycerides (toxicity)

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