Acute inhalation exposure to vaporized methamphetamine causes lung injury in mice

Sandra M. Wells, Mary C. Buford, Sarah N. Braseth, James D. Hutchison, Andrij Holian

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

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)-α 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.

Original languageEnglish (US)
Pages (from-to)829-838
Number of pages10
JournalInhalation Toxicology
Volume20
Issue number9
DOIs
StatePublished - Jul 2008
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported in part by the National Center for Research Resources (NCRR; P20RR017670 to A. H.) and the National Heart, Lung, and Blood Institute (NHLBI; 1F32HL086154 to S. M. W.), both components of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and not necessarily the official views of NCRR, NHLBI, or NIH. The authors thank R. Hamilton for statistical support, L. Hoerner for technical assistance with the laboratory animals, and P. Shaw for technical assistance with the LSC measurements. In addition, we thank A. Harris and B. Klietz at the Montana State Crime Laboratory for their technical assistance with the development of the exposure model.

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