title: Involvement of serotonin mechanism in methamphetamine-induced chronic pulmonary toxicity in rats.
abstract: The widest distribution and the highest uptake of methamphetamine (MA) in the human body occurred in the lungs, so that more and more attention should be paid to MA-induced pulmonary toxicity. MA induces the release of serotonin, which is an important mediator in pulmonary disease. The purpose of this study is to investigate the chronic response of the lung to MA and its potential mechanism in rats. Models of the chronic toxicity of MA were established with MA of 5 mg/kg and 10 mg/kg (intraperitoneally, twice per day) for 5 weeks. It was found that the high dose of MA induced rat pulmonary toxicity: crowded lung parenchyma, thickened septum, reduced number of alveolar sacs, inflammatory cell infiltration, and pulmonary arteriolar remodeling. In addition, MA resulted in a significant increase in the lung serotonin concentration and the marked upregulation of tryptophan hydroxylase 1, vesicular monoamine transporter 2, serotonin transporter, and downregulation of monoamine oxidase-A. These findings suggest that MA induced chronic pulmonary toxicity, which is concerned with the elevated serotonin concentration in rat lungs by increased synthesis, reduced metabolism, augmented accumulation, and promoted release of serotonin.
authors.affiliation: Department of Clinical Pharmacology, China Medical University, Shenyang, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.forename: H M
authors.initials: HM
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Bai
authors.forename: X H
authors.initials: XH
authors.lastname: Zhang
authors.forename: Y X
authors.initials: YX
authors.lastname: Sun
authors.forename: H L
authors.initials: HL
authors.lastname: Wang
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D008995:Monoamine Oxidase / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
chemical_list: D016601:RNA-Binding Proteins; C482440:Sert1 protein, rat; C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins; D012701:Serotonin; D008694:Methamphetamine; D014365:Tryptophan Hydroxylase; C504570:tph1 protein, rat; D008995:Monoamine Oxidase
keywords: Methamphetamine; chronic pulmonary toxicity; inflammation; pulmonary arterial hypertension; remodeling; serotonin