Rolipram attenuates bleomycin A5-induced pulmonary fibrosis in rats.
OBJECTIVE
Pulmonary fibrosis has a poor prognosis. The pathogenesis of fibrotic disorders is unclear, but the extent of lung damage due to persistent inflammation is regarded as a critical factor. Rolipram inhibits inflammation induced by various stimuli, as well as the chemotaxis of fibroblasts. In this study rolipram was used to treat pulmonary fibrosis induced by bleomycin A5 in rats, and the possible mechanisms were investigated.


METHODS
Rolipram (0.25 mg/kg) was administered intraperitoneally daily, following intratracheal instillation of bleomycin A5 (5 mg/kg). Animals were killed at 7 or 28 days after bleomycin A5 instillation, and indices of lung damage and fibrosis were evaluated.


RESULTS
Bleomycin A5 induced pulmonary inflammation and fibrosis, increased the levels of malondialdehyde and tumour necrosis factor-alpha and enhanced accumulation of collagen in the lungs. Rolipram administration significantly attenuated these effects.


CONCLUSIONS
Rolipram ameliorated pulmonary inflammation and fibrosis induced by bleomycin A5 in rats. The effects of rolipram may be associated with its antioxidant activity and inhibition of tumour necrosis factor-alpha production.
Pan
Jin Bing
JB
Department of Respiratory Medicine, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Hou
Yu Hong
YH
Zhang
Guo Jun
GJ
D000818:Animals; D001761:Bleomycin / Q000009:adverse effects / Q000031:analogs & derivatives*; D000242:Cyclic AMP / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D054990:Idiopathic Pulmonary Fibrosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D020889:Rolipram / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; D008315:Malondialdehyde; C025703:bleomycetin; D000242:Cyclic AMP; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram; D006909:Hydroxyproline