Vesnarinone represses the fibrotic changes in murine lung injury induced by bleomycin.
We investigated the potential usefulness of vesnarinone, a novel cytokine inhibitor, for the treatment of lung fibrosis using a murine model of bleomycin (BLM)-induced pulmonary fibrosis. Mice were fed a control diet (n=42), or a diet containing low (n=42) or high (n=42) dose of vesnarinone. Dietary intake of vesnarinone minimized the BLM toxicity as reflected by significant decreases in numbers of inflammatory cells, KC, and soluble TNF receptors in the bronchoalveolar lavage fluid. A quantitative evaluation of histology demonstrated significantly mild lung parenchymal lesions in BLM-treated mice fed with diet containing high dose of vesnarinone than in the control diet group. Consistent with the histopathology, hydroxyproline levels in lung tissue from BLM-treated mice fed with diet containing vesnarinone were significantly lower than that from mice fed with control diet. We concluded that vesnarinone inhibits BLM-induced pulmonary fibrosis, at least in part, by the inhibition of acute lung injuries in the early phase.
Inage
Minoru
M
First Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan.
Nakamura
Hidenori
H
Saito
Hiroshi
H
Abe
Shuichi
S
Hino
Toshihiko
T
Takabatake
Noriaki
N
Terashita
Kyoko
K
Ogura
Manabu
M
Kato
Shuichi
S
Hosokawa
Tetsumi
T
Sata
Makoto
M
Tomoike
Hitonobu
H
D000818:Animals; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016207:Cytokines / Q000037:antagonists & inhibitors*; D004032:Diet; D006820:Hyaluronic Acid / Q000097:blood; D006909:Hydroxyproline / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011719:Pyrazines; D011804:Quinolines / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D012720:Severity of Illness Index
D016207:Cytokines; D011719:Pyrazines; D011804:Quinolines; D018124:Receptors, Tumor Necrosis Factor; D001761:Bleomycin; C041667:vesnarinone; D006820:Hyaluronic Acid; D006909:Hydroxyproline