ethionamide and Fatty-Liver

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.

Topics: Animals; Biomarkers; Ethionamide; Fatty Liver; Humans; Liver; Phosphatidylcholines; Rats; Triglycerides

Topics: Acetates; Animals; Carbon Isotopes; Ethionamide; Fatty Liver; Glucosephosphate Dehydrogenase; Lipids; Liver; Male; Rats; Stimulation, Chemical; Time Factors

Topics: Animals; Carbon Tetrachloride; Cholesterol; Ethionamide; Fatty Liver; Liver; Male; Rats; Transaminases

Topics: Animals; Carbon Tetrachloride; Chromatography, Gas; Ethionamide; Fatty Acids; Fatty Liver; Liver; Rats; Time Factors

Topics: Adipose Tissue; Animals; Epididymis; Ethionamide; Fatty Acids; Fatty Acids, Nonesterified; Fatty Liver; Male; Rats

Topics: Animals; Ethionamide; Fatty Acids; Fatty Liver; Glucosephosphate Dehydrogenase; Isocitrate Dehydrogenase; Liver; Malate Dehydrogenase; Male; NADP; Pyrazinamide; Rats

Topics: Animals; Ethionamide; Fatty Acids; Fatty Liver; Male; Mitochondria, Liver; Oxidoreductases; Rats

Topics: Bile Acids and Salts; Bilirubin; Biopsy; Chemical and Drug Induced Liver Injury; Ethionamide; Fatty Liver; Humans; Liver Diseases; Pyrazinamide; Transaminases; Tuberculosis, Miliary; Tuberculosis, Pulmonary

Topics: Chemical and Drug Induced Liver Injury; Choline; Ethionamide; Fatty Liver; Hepatitis; Nucleosides; Promethazine; Pyridoxal Phosphate; Rats; Research; Toxicology