title: Methamphetamine causes acute hyperthermia-dependent liver damage.
abstract: Methamphetamine-induced neurotoxicity has been correlated with damage to the liver but this damage has not been extensively characterized. Moreover, the mechanism by which the drug contributes to liver damage is unknown. This study characterizes the hepatocellular toxicity of methamphetamine and examines if hyperthermia contributes to this liver damage. Livers from methamphetamine-treated rats were examined using electron microscopy and hematoxylin and eosin staining. Methamphetamine increased glycogen stores, mitochondrial aggregation, microvesicular lipid, and hydropic change. These changes were diffuse throughout the hepatic lobule, as evidenced by a lack of hematoxylin and eosin staining. To confirm if these changes were indicative of damage, serum aspartate and alanine aminotransferase were measured. The functional significance of methamphetamine-induced liver damage was also examined by measuring plasma ammonia. To examine the contribution of hyperthermia to this damage, methamphetamine-treated rats were cooled during and after drug treatment by cooling their external environment. Serum aspartate and alanine aminotransferase, as well as plasma ammonia were increased concurrently with these morphologic changes and were prevented when methamphetamine-induced hyperthermia was blocked. These findings support that methamphetamine produces changes in hepatocellular morphology and damage persisting for at least 24 h after drug exposure. At this same time point, methamphetamine treatment significantly increases plasma ammonia concentrations, consistent with impaired ammonia metabolism and functional liver damage. Methamphetamine-induced hyperthermia contributes significantly to the persistent liver damage and increases in peripheral ammonia produced by the drug.
authors.affiliation: Department of Neurosciences, University of Toledo College of Medicine 3000 Arlington Ave., Toledo, Ohio, 43614.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Halpin
authors.affiliation: Department of Pathology, University of Toledo College of Medicine 3000 Arlington Ave., Toledo, Ohio, 43614.
authors.forename: William T
authors.initials: WT
authors.lastname: Gunning
authors.affiliation: Department of Neurosciences, University of Toledo College of Medicine 3000 Arlington Ave., Toledo, Ohio, 43614.
authors.forename: Bryan K
authors.initials: BK
authors.lastname: Yamamoto
keywords: Ammonia; hyperthermia; liver damage; methamphetamine