Beneficial effects of early (but not late) intervention of heme oxygenase-1 on bleomycin-induced pulmonary fibrosis in mice.
The aim of this study is to explore the effects of early and late intervention in heme oxygenase-1 (HO-1) expression or activity on pulmonary fibrosis in mice. Mice were divided into four groups: one control and three bleomycin hydrochloride-induced groups in which mice were administered phosphate-buffered saline (PBS), hemin or Cr (III) mesoporphyrin IX chloride (CrMP). Early intervention with hemin, an HO-1 inducer, abrogated bleomycin-induced pulmonary fibrosis (fibrotic/reparative score decrease from 21.0±2.4 to 13.8±1.7, P<0.01), and early intervention with CrMP, an HO-1 inhibitor, worsened bleomycin-induced pulmonary fibrosis (fibrotic/reparative score increase from 21.0±2.4 to 32.5±2.9, P<0.01). Elevated glutathione expression and reduced expression of TGF-β1, hydroxyproline, LDH and MDA were seen in the lungs of the early hemin intervention group compared to that seen in the PBS group (P<0.05). These results taken together show that HO-1 can prevent or ameliorate pulmonary fibrosis and oxidative stress and inflammation at an early stage of pulmonary fibrosis.
Respiratory Department, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Chengzhen
C
Jin
Dan
D
Zhou
Fuzhen
F
Lv
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors*; D006427:Hemin / Q000494:pharmacology; D006909:Hydroxyproline / Q000378:metabolism; D045022:Lactate Dehydrogenases / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008665:Metalloporphyrins / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D008665:Metalloporphyrins; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D008315:Malondialdehyde; D006427:Hemin; D045022:Lactate Dehydrogenases; D051547:Heme Oxygenase-1; D005978:Glutathione; D006909:Hydroxyproline