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

Autor: Muta K; Toxicology Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Yokohama, Japan., Saito K; Division of Medicinal Safety Science, National Institute of Health Sciences, Kawasaki, Japan., Kemmochi Y; Toxicology Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Yokohama, Japan., Masuyama T; Toxicology Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Yokohama, Japan., Kobayashi A; Toxicology Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Yokohama, Japan., Saito Y; Division of Medicinal Safety Science, National Institute of Health Sciences, Kawasaki, Japan., Sugai S; Toxicology Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Yokohama, Japan.
Jazyk: angličtina
Zdroj: Journal of applied toxicology : JAT [J Appl Toxicol] 2022 Sep; Vol. 42 (9), pp. 1533-1547. Date of Electronic Publication: 2022 Mar 29.
DOI: 10.1002/jat.4324
Abstrakt: 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.
(© 2022 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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