Effects of aminoguanidine and antioxidant erdosteine on bleomycin-induced lung fibrosis in rats.
Reactive oxygen and nitrogen species have been implicated in the pathogenesis of bleomycin-induced lung fibrosis. The effects of aminoguanidine and erdosteine on the bleomycin-induced lung fibrosis were evaluated in rats. The animals were placed into five groups: Vehicle + vehicle, vehicle + bleomycin (2.5 U/kg), bleomycin + aminoguanidine (200 mg/kg), bleomycin + erdosteine (10 mg/kg), and bleomycin + erdosteine + aminoguanidine. Bleomycin administration resulted in prominent lung fibrosis as measured by lung hydroxyproline content and lung histology, which is completely prevented by erdosteine and aminoguanidine. A strong staining for nitro tyrosine antibody in lung tissue and increased levels of lung NO were found in bleomycin group, that were significantly reduced by aminoguanidine and erdosteine. Aminoguanidine and erdosteine significantly prevented depletion of superoxide dismutase and glutathione peroxidase and elevated myeloperoxidase activities, malondialdehyde level in lung tissue produced by bleomycin. Data presented here indicate that aminoguanidine and erdosteine prevented bleomycin-induced lung fibrosis and that nitric oxide mediated tyrosine nitration of proteins plays a significant role in the pathogenesis of bleomycin-induced lung fibrosis. Also our data suggest that antifibrotic affect of antioxidants may be due to their inhibitory effect on nitric oxide generation in this model.
Yildirim
Zeki
Z
Medical Faculty, Department of Pulmonary Medicine, Inonu University, 44069 Malatya, Turkey. zyildirim@inonu.edu.tr
Turkoz
Yusuf
Y
Kotuk
Mahir
M
Armutcu
Ferah
F
Gurel
Ahmet
A
Iraz
Mustafa
M
Ozen
Suleyman
S
Aydogdu
Ismet
I
Akyol
Omer
O
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001761:Bleomycin / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D005979:Glutathione Peroxidase / Q000032:analysis; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D009569:Nitric Oxide / Q000032:analysis; D009195:Peroxidase / Q000032:analysis; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000032:analysis; D013864:Thioglycolates / Q000494:pharmacology / Q000627:therapeutic use; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis
D000975:Antioxidants; D006146:Guanidines; D013864:Thioglycolates; D013876:Thiophenes; D001761:Bleomycin; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; C048498:erdosteine; D009195:Peroxidase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C004479:pimagedine