title: Dimethylthiourea decreases acute pulmonary edema induced by phorbol myristate acetate in isolated blood-perfused lung of the rat.
abstract: Acute pulmonary edema can be induced by phorbol myristate acetate (PMA). Oxygen radicals released from the neutrophils have been considered to play an important role in the pathogenesis of PMA-induced pulmonary edema. In the present experiment, we studied the effect of dimethylthiourea (DMTU) on PMA-induced pulmonary injuries in isolated perfused lungs of rats. DMTU is a potent scavenger of the hydroxyl radical and hydrogen peroxide. PMA infusion into the isolated lung increased pulmonary arterial pressure (delta PAP) by 37.8 +/- 3.9 mmHg. The lung weight gain (LWG) and lavage albumin concentration (LAC) amounted to 6.2 +/- 1.2 g and 102.0 +/- 22.9 mg/dl, respectively. DMTU (100 mM) pretreatment significantly reduced the PAP increase (delta PAP = 4.6 +/- 0.8 mmHg, p less than 0.001), LWG (0.3 +/- 0.1 g, p less than 0.01) and LAC (25.3 +/- 1.7 mg/dl, p less than 0.01). Additional in vitro experiments demonstrated that DMTU depressed the chemiluminescence released from neutrophils activated by PMA (17.9 +/- 2.6 mV.min to 2.6 +/- 0.5 mV.min, p less than 0.01). The results suggest that DMTU, a scavenger of toxic radicals, decreases the lung edema through both attenuation of pulmonary hypertension and protection of vascular permeability from PMA injury.
authors.affiliation: Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: C L
authors.initials: CL
authors.lastname: Chou
authors.forename: H I
authors.initials: HI
authors.lastname: Chen
authors.forename: K
authors.initials: K
authors.lastname: Hsu
authors.forename: M H
authors.initials: MH
authors.lastname: Li
authors.forename: D
authors.initials: D
authors.lastname: Wang
mesh_terms: D000208:Acute Disease; D000818:Animals; D001804:Blood Transfusion, Autologous; D005609:Free Radicals; D066298:In Vitro Techniques; D007958:Leukocyte Count; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D009929:Organ Size; D011654:Pulmonary Edema / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D005609:Free Radicals; C038983:1,3-dimethylthiourea; D013890:Thiourea; D013755:Tetradecanoylphorbol Acetate