A specific chymase inhibitor, NK3201, suppresses bleomycin-induced pulmonary fibrosis in hamsters.
We evaluated whether a chymase inhibitor, 2-(5-formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidine-1-yl)-N-[(3,4-dioxo-1-phenyl-7-(2-pyridyloxy))-2-heptyl]acetamide (NK3201), suppressed bleomycin-induced pulmonary fibrosis. Hamsters were orally administered NK3201 (30 mg/kg per day) or placebo, beginning 5 days before intratracheal instillation of bleomycin (10 mg/kg). Four weeks after the instillation of bleomycin, pulmonary chymase activity in placebo-treated hamsters was significantly higher than in control hamsters, whereas the activity in NK3201-treated hamsters was significantly lower than in placebo-treated hamsters. The ratio of fibrotic area to total area in NK3201-treated hamsters was significantly decreased to 54.0% of the ratio in placebo-treated hamsters. Therefore, NK3201 may be useful in the prevention of pulmonary fibrosis.
Sakaguchi
Masato
M
Department of Pharmacology, Osaka Medical College, Takatsuki City, Osaka 589-8686, Japan.
Takai
Shinji
S
Jin
Denan
D
Okamoto
Yukiko
Y
Muramatsu
Michiko
M
Kim
Shokei
S
Miyazaki
Mizuo
M
D000081:Acetamides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000284:Administration, Oral; D000818:Animals; D001761:Bleomycin / Q000009:adverse effects*; D053818:Chymases; D024061:Collagen Type III / Q000187:drug effects / Q000235:genetics; D006224:Cricetinae; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007564:Japan; D008168:Lung / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D008297:Male; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000737:chemistry / Q000187:drug effects / Q000235:genetics; D012697:Serine Endopeptidases / Q000737:chemistry / Q000187:drug effects*; D014020:Tissue Extracts / Q000737:chemistry
D000081:Acetamides; D024061:Collagen Type III; D004791:Enzyme Inhibitors; C437945:NK3201; D011743:Pyrimidines; D012333:RNA, Messenger; D014020:Tissue Extracts; D001761:Bleomycin; D012697:Serine Endopeptidases; D053818:Chymases