title: Serum metabolic changes in rats after intragastric administration of dextromethorphan.
abstract: Dextromethorphan is recognized as a substance of abuse around the world. An estimated 3.1 million people between the ages of 12 and 25 years (5.3%) misused over-the-counter cough and cold medications in 2006. In this study, we developed a serum metabolomic method by gas chromatography-mass spectrometry (GC-MS) to evaluate the effect of abuse of dextromethorphan on rats. The dextromethorphan-treated rats were given 12, 24 and 48 mg/kg (low, medium, high) of dextromethorphan by intragastric administration each day for 3 days. Partial least squares-discriminate analysis revealed that intragastric administration of dextromethorphan induced metabolic perturbations. Compared with the control (healthy) group, the levels of propanoic acid, urea, heptafluorobutanoic acid, 2-hexyldecanoic acid and butanedioic acid of the low group decreased; levels of propanoic acid and heptafluorobutanoic acid of the medium group decreased, while that of benzoic acid increased; and levels of 2-hexyldecanoic acid, glycerol and butanedioic acid of the high group increased. These biomarkers are involved in the citric acid cycle, urea cycle, glycerolipid metabolism and tricarboxylic acid cycle. The results indicate that the metabolomic method by GC-MS may be useful to elucidate abuse of dextromethorphan. According to the pathological changes in the liver at different dosages, dextromethorphan is not hepatotoxic after intragastric administration of 12, 24 and 48 mg/kg for 3 days.
authors.affiliation: The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China.
authors.forename: Shihui
authors.initials: S
authors.lastname: Bao
authors.affiliation: Anlytical and Testing Center of Wenzhou Medical University, Wenzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Anlytical and Testing Center of Wenzhou Medical University, Wenzhou, China.
authors.forename: Zixia
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Anlytical and Testing Center of Wenzhou Medical University, Wenzhou, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Su
authors.affiliation: Anlytical and Testing Center of Wenzhou Medical University, Wenzhou, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Mo
authors.affiliation: Anlytical and Testing Center of Wenzhou Medical University, Wenzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Hong
authors.affiliation: Anlytical and Testing Center of Wenzhou Medical University, Wenzhou, China.
authors.forename: Shuyi
authors.initials: S
authors.lastname: Qian
authors.affiliation: Department of Pharmacy, Wenzhou People's Hospital, Wenzhou, China.
authors.forename: Lianguo
authors.initials: L
authors.lastname: Chen
authors.affiliation: Anlytical and Testing Center of Wenzhou Medical University, Wenzhou, China.
authors.forename: Fa
authors.initials: F
authors.lastname: Sun
authors.affiliation: Anlytical and Testing Center of Wenzhou Medical University, Wenzhou, China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Wen
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wu
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Lufeng
authors.initials: L
authors.lastname: Hu
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Guanyang
authors.initials: G
authors.lastname: Lin
authors.affiliation: Anlytical and Testing Center of Wenzhou Medical University, Wenzhou, China.
authors.forename: Xianqin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D002952:Citric Acid Cycle; D003652:Decanoic Acids / Q000097:blood; D003915:Dextromethorphan / Q000008:administration & dosage* / Q000494:pharmacology*; D008401:Gas Chromatography-Mass Spectrometry; D005990:Glycerol / Q000097:blood; D016018:Least-Squares Analysis; D008297:Male; D055432:Metabolomics / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019802:Succinic Acid / Q000097:blood
chemical_list: D003652:Decanoic Acids; C400263:2-hexyldecanoic acid; D003915:Dextromethorphan; D019802:Succinic Acid; D005990:Glycerol
keywords: GC-MS; abuse rat; dextromethorphan; metabolomics