Free radicals mediate amphetamine-induced acute pulmonary edema in isolated rat lung.
Intravenous amphetamine abuse may cause serious cardiopulmonary complications via unknown mechanisms. We investigated the role of free radicals in the amphetamine-induced lung injury using isolated rat lungs. Adding amphetamine into the perfusate caused dose-dependent increases in perfusion pressure and lung weight. Amphetamine increased the filtration coefficient (K(f)) by 90 +/- 20% and 210 +/- 10% at doses of 10 microM and 50 microM, respectively, as compared to the baseline level. Pretreatment with dimethylthiourea (DMTU), an oxygen radical scavenger, abolished the pulmonary hypertension, lung weight gain, and permeability changes. We also examined the effect of amphetamine on free radical generation in polymorphonuclear leukocytes (PMN). Adding phorbol myristate acetate (PMA, 1 nM) enhanced the chemiluminescence indicating the functional viability of the isolated PMN. Amphetamine (50 microM) significantly enhanced the chemiluminescence generation of PMN by 152 +/- 26% as compared with the baseline value. Combination of amphetamine and PMA increased free radical formation by 360 +/- 85%. In summary, our results showed that amphetamine may cause acute lung injury by overproduction of free radicals. Although amphetamine can activate PMN, the source of free radicals remains to be determined.
Huang
Kun-Lun
KL
Institute of Undersea and Hyperbaric Medicine, National Defense Medical Center, Taipei, Taiwan, ROC.
Shaw
Kai-Ping
KP
Wang
David
D
Hsu
Kang
K
Huang
Tze-Shung
TS
Chen
Hsing-I
HI
D000208:Acute Disease; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D003913:Dextroamphetamine / Q000633:toxicity*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism*; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D009929:Organ Size; D011652:Pulmonary Circulation / Q000187:drug effects; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
D016166:Free Radical Scavengers; D005609:Free Radicals; C038983:1,3-dimethylthiourea; D013890:Thiourea; D003913:Dextroamphetamine