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 mechanismrelated biomarkers for ETH-induced hepatic steatosis.

Changes in liver metabolic pathways demonstrate efficacy of the combined dietary and microbial therapeutic intervention in MASLD mouse model

“…Changes in other glycerophospholipids such as the increased levels of LPC (22:1) which is known to be decreased in mice fed with HFD [ 55 ], respectively, and a decrease of lysophosphatidylinositol (20:4), which is increased in the plasma of obese subjects [ 56 ], further support the beneficial effects of EcNA in MASLD. Furthermore, the EcNA intervention decreased PC (18:0/20:4), a potential biomarker to predict ethionamide-induced hepatic steatosis in rats [ 57 ]. Nevertheless, the role of other significantly changed lipids such as LPE (17:0), LPE (17:1), and LPE (18:0) need to be further investigated in the context of MASLD.…”