Acute inhalation exposure to vaporized methamphetamine causes lung injury in mice.
Methamphetamine (MA) is currently the most widespread illegally used stimulant in the United States. Use of MA by smoking is the fastest growing mode of administration, which increases concerns about potential pulmonary and other medical complications. A murine exposure system was developed to study the pulmonary affects of inhaled MA. Mice were exposed to 25-100 mg vaporized MA and assessments were made 3 h following initiation of exposure to model acute lung injury. Inhalation of MA vapor resulted in dose-dependent increases in MA plasma levels that were in the range of those experienced by MA users. At the highest MA dose, histological changes were observed in the lung and small but significant increases in lung wet weight to body weight ratios (5.656 +/- 0.176 mg/g for the controls vs. 6.706+/- 0.135 mg/g for the 100 mg MA-exposed mice) were found. In addition, there was 53% increase in total protein in bronchoalveolar lavage (BAL) fluid, greater than 20% increase in albumin levels in the BAL fluid, greater than 2.5-fold increase in lactate dehydrogenase levels in the BAL fluid, and reduced total BAL cell numbers (approximately 77% of controls). Levels of the early response cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 were dose-dependently increased in BAL fluid of MA-exposed mice. Exposure to 100 mg MA significantly increased free radical generation in the BAL cells to 107-146% of controls and to approximately 135% of the controls in lung tissue in situ. Together, these data show that acute inhalation exposure to relevant doses of volatilized MA is associated with elevated free radical formation and significant lung injury.
Wells
Sandra M
SM
Center for Environmental Health Sciences, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, Montana 59812, USA. sandra.wells@umontana.edu
Buford
Mary C
MC
Braseth
Sarah N
SN
Hutchison
James D
JD
Holian
Andrij
A
D000208:Acute Disease; D000280:Administration, Inhalation; D000418:Albumins / Q000032:analysis; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000032:analysis
D000418:Albumins; D000697:Central Nervous System Stimulants; D016207:Cytokines; D017382:Reactive Oxygen Species; D008694:Methamphetamine; D007770:L-Lactate Dehydrogenase