title: Neurotoxicity induced by methamphetamine-heroin combination in PC12 cells.
abstract: Simultaneous administration of psychostimulants and opioids is a major drug abuse problem worldwide. The combination of psychostimulants and opioids produces more serious effects than either drug alone and is responsible for numerous deaths. In recent years, owing to its increased use, methamphetamine (METH), a psychostimulant, has become a popular choice for use in combination with opioids, especially heroin. However, little is known about the neurotoxicity of METH/heroin combination. The aims of this study were to evaluate whether METH/heroin combination was more neurotoxic than either drug alone and analyze the possible neurotoxic mechanisms using rat pheochromocytoma (PC12) cells. Our data showed that METH/heroin combination exhibited a significant decrease in cell viability than either drug alone, and the coefficient of drug interaction (CDI) indicated that the combination appeared to produce synergistic effects. Further studies showed that METH/heroin combination induced apoptosis and decreased the mitochondrial potential significantly, compared to either drug alone. This was demonstrated by a significant decrease in the expression of Bcl-2 and an increase in expression of Bax, accompanied by increase in the activities of caspase-3 and caspase-9. These results suggest that the combination of METH and heroin is more neurotoxic than either drug alone, and it induces apoptosis via the mitochondrial apoptotic pathway.
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan 430056, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Tian
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan 430056, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Ru
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan 430056, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xiong
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan 430056, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Yue
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan 430056, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan 430056, China.
authors.forename: Baomiao
authors.initials: B
authors.lastname: Ma
authors.affiliation: Wan Ji Psychiatric Hospital, Wuhan, 430051, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Gan
authors.affiliation: Wan Ji Psychiatric Hospital, Wuhan, 430051, China.
authors.forename: Yuanren
authors.initials: Y
authors.lastname: Si
authors.affiliation: Wan Ji Psychiatric Hospital, Wuhan, 430051, China.
authors.forename: Huqiao
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan 430056, China. Electronic address: licy.whibs.corresp@outlook.com.
authors.forename: Chaoying
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D004357:Drug Synergism; D003932:Heroin / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008694:Methamphetamine / Q000633:toxicity*; D009294:Narcotics / Q000633:toxicity*; D016716:PC12 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats
chemical_list: D000697:Central Nervous System Stimulants; D009294:Narcotics; D019253:Proto-Oncogene Proteins c-bcl-2; D008694:Methamphetamine; D003932:Heroin; D053148:Caspase 3; D053453:Caspase 9
keywords: Combination; Heroin; Methamphetamine; Neurotoxicity; PC12 cells