title: Metabolic changes in rats after intragastric administration of MGCD0103 (Mocetinostat), a HDAC class I inhibitor.
abstract: MGCD0103, an isotype-selective HDACi, has been clinically evaluated for the treatment of hematologic malignancies and advanced solid tumors, alone and in combination with standard-of-care agents. 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 MGCD0103 on rats. The MGCD0103 group rats were given 20, 40, 80 mg/kg of MGCD0103 by intragastric administration each day for 7 days. Pattern recognition analysis, including both principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) revealed that intragastric administration of MGCD0103 induced metabolic perturbations. As compared to the control group, the levels of L-alanine, L-isoleucine, and L-leucine of MGCD0103 group decreased. The results indicate that metabolomic methods based on GC-MS may be useful to elucidate side effect of MGCD0103 through the exploration of biomarkers (L-alanine, L-isoleucine, and L-leucine). According to the pathological changes of liver at difference dosage, MGCD0103 is hepatotoxic and its toxity is dose-dependent.
authors.affiliation: Shanghai Institute of Pharmaceutical Industry Shanghai 200437, China.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Critical Care and Pain Medicine, The Second Affiliated Hospital, Wenzhou Medical University Wenzhou 325000, China.
authors.forename: Haiya
authors.initials: H
authors.lastname: Wu
authors.affiliation: Laboratory Animal Centre, Wenzhou Medical University Wenzhou 325035, China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Wen
authors.affiliation: Laboratory Animal Centre, Wenzhou Medical University Wenzhou 325035, China.
authors.forename: Fa
authors.initials: F
authors.lastname: Sun
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325000, China.
authors.forename: Xuezhi
authors.initials: X
authors.lastname: Yang
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325000, China.
authors.forename: Lufeng
authors.initials: L
authors.lastname: Hu
mesh_terms: D000409:Alanine / Q000097:blood*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D007532:Isoleucine / Q000097:blood*; D007930:Leucine / Q000097:blood*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D055432:Metabolomics; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001549:Benzamides; D015415:Biomarkers; D056572:Histone Deacetylase Inhibitors; D011743:Pyrimidines; D007532:Isoleucine; C523184:mocetinostat; D007930:Leucine; D000409:Alanine
keywords: GC/MS; MGCD0103; Metabolomics; rat