Halofuginone does not reduce fibrosis in bleomycin-induced lung injury.
Halofuginone, a coccidiostatic alkaloid, has anti-fibrotic properties, and may be useful as a therapeutic agent in lung fibrosis. To test this hypothesis we investigated the effect of halofuginone on bleomycin-induced lung fibrosis in Sprague-Dawley rats. Treatment groups included: (1) a single intratracheal (IT) instillation of 1.2U bleomycin, and intraperitoneal (IP) injection of halofuginone (0.5 mg/dose), every other day; (2) IT 1.2U bleomycin and IP distilled water (D.W.), every other day; (3) IT 0.8U bleomycin and daily IP halofuginone (0.5 mg/dose); (4) IT 0.8U bleomycin and daily IP D.W.; (5) IT saline and IP halofuginone, every other day; (6) IT saline and daily IP D.W.; (7) IT 0.625U bleomycin and oral halofuginone (10 mg/kg rodent lab chow); (8) IT 0.625U bleomycin and standard lab chow. Animals were studied 14 days after IT instillation. Lung injury was evaluated by total and differential cell count in bronchoalveolar lavage fluid, by a semi-quantitative morphological index of lung injury, and by biochemical analysis of lung hydroxyproline content. Overt signs of lung injury were apparent in bleomycin-treated rats by all measures. These changes were not affected by treatment with halofuginone, irrespective of the treatment regimen used. This study does not support the use of halofuginone to prevent or ameliorate lung fibrosis.
Lung Cellular and Molecular Biology Laboratory-Institute of Pulmonology, Hadassah University Hospital and the Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Anat
A
Tzurel
Michael J
MJ
Segel
Reuven
R
Or
Ronald H
RH
Goldstein
Raphael
R
Breuer
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D001761:Bleomycin / Q000633:toxicity*; D015152:Blotting, Northern; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D007442:Intubation, Intratracheal; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008297:Male; D010880:Piperidines; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D011799:Quinazolines / Q000627:therapeutic use*; D052999:Quinazolinones; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000964:Antimetabolites, Antineoplastic; D010880:Piperidines; D011799:Quinazolines; D052999:Quinazolinones; D016212:Transforming Growth Factor beta; D001761:Bleomycin; D012313:RNA; D003094:Collagen; C010176:halofuginone; D006909:Hydroxyproline