Serum metabolic changes in rats after intragastric administration of entinostat

Entinostat, also known as SNDX-275 and MS-275, is a benzamide histone deacetylase inhibitor undergoing clinical trials for treatment of various cancers. In this study, we developed a serum metabolomic method based on gas chromatography-mass spectrometry (GC-MS) to evaluate the effect of intragastric administration of entinostat on rats. The entinostat group rats were given 12.3, 49 mg/kg of entinostat by intragastric administration each day for 7 days. Partial least squares-discriminate analysis (PLS-DA) revealed that intragastric administration of entinostat induced metabolic perturbations. Compared to the control group, the level of butanedioic acid of entinostat group decreased. The results indicate that metabolomic methods based on GC-MS may be useful to elucidate side effect of entinostat through the exploration of biomarkers (butanedioic acid). According to the pathological changes of liver at difference dosage, entinostat is hepatotoxic and its toxity is dose-dependent.