The effect of suramin on bleomycin-induced lung injury.
Since transforming growth factor beta (TGF-beta) is presumed to play a role in lung fibrosis, we evaluated the effect of suramin (Sur), a substance with an anti-TGF-beta effect, in vivo on bleomycin (Bleo)-induced pulmonary injury in mice and in vitro on human lung fibroblasts. Four groups of C57BL/6 mice each received one of four treatments: (1) intratracheal (i.t.) instillation of Bleo and intraperitoneal (i.p.) injections of Sur, every other day, starting one day before i.t. instillation of Bleo (Bleo-Sur); (2) i.t. Bleo and i.p. injections of saline (Bleo-Sal); (3) i.t. saline and i.p. Sur (Sal-Sur); and (4) i.t. and i.p. saline (Sal-Sal). Animals were sacrificed 14 days after i.t. treatment. Lung injury was evaluated by analysis of bronchoalveolar lavage (BAL) fluid, histologically by the semiquantitative morphological index, and biochemically by analysis of lung hydroxyproline content. In vitro, Sur did not affect TGF-beta induced increase of alpha1 (I) collagen mRNA in human lung fibroblasts. In vivo treatment of mice with Sur did not affect Bleo-induced lung injury. These results indicate that despite its potential anti TGF-beta and lymphocytotoxic effects, Sur is not a therapeutic candidate drug for rescue of lung fibrosis.
Lossos
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IS
Lung Cellular & Molecular Biology Laboratory-Institute of Pulmonology, Hadassah University Hospital and Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Izbicki
G
G
Or
R
R
Goldstein
R H
RH
Breuer
R
R
D000818:Animals; D001761:Bleomycin / Q000008:administration & dosage / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002460:Cell Line; D003094:Collagen / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007274:Injections, Intraperitoneal; D007322:Instillation, Drug; D008156:Luciferases / Q000235:genetics; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology; D013498:Suramin / Q000008:administration & dosage / Q000494:pharmacology*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000494:pharmacology
D016212:Transforming Growth Factor beta; D001761:Bleomycin; D013498:Suramin; D003094:Collagen; D008156:Luciferases