title: Caffeine potentiates methamphetamine-induced toxicity both in vitro and in vivo.
abstract: Ya-Ba, a combination of the two potent psychostimulants methamphetamine (METH) and caffeine (CAF), is commonly used by drug abusers in Thailand and neighboring countries. While the neurotoxic effects of METH are well documented, the toxicity of this combination is mostly unknown. This study aimed to elucidate the effects of this particular drug combination using both in vitro and in vivo models. We found that combined treatment of METH and CAF at individually non-toxic concentrations significantly decreased viability of human neuroblastoma SK-N-SH cells. The reduction in cell survival was accompanied by an increase in reactive oxygen species (ROS) formation and the Bax/Bcl-2 ratio. In vivo data showed that combined administration of METH and CAF increased the mortality rate of rats, with an increase in the level of thiobarbituric acid reactive substances (TBARS), the indicator of oxidative stress, in striatal tissues. The results indicate that caffeine potentiates the toxic effects of methamphetamine, possibly via a mechanism involving an increase in dopamine release and excess ROS generation.
authors.affiliation: Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Theerin
authors.initials: T
authors.lastname: Sinchai
authors.forename: Surin
authors.initials: S
authors.lastname: Plasen
authors.forename: Yupin
authors.initials: Y
authors.lastname: Sanvarinda
authors.forename: Yamaratee
authors.initials: Y
authors.lastname: Jaisin
authors.forename: Piyarat
authors.initials: P
authors.lastname: Govitrapong
authors.forename: Noppawan Phumala
authors.initials: NP
authors.lastname: Morales
authors.forename: Piyanee
authors.initials: P
authors.lastname: Ratanachamnong
authors.forename: Duangporn
authors.initials: D
authors.lastname: Plasen
mesh_terms: D000818:Animals; D002110:Caffeine / Q000008:administration & dosage / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000633:toxicity*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004357:Drug Synergism; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000633:toxicity*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000697:Central Nervous System Stimulants; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D051028:bcl-2-Associated X Protein; D002110:Caffeine; D008694:Methamphetamine