Evaluation of the antifibrotic effect of fenofibrate and rosiglitazone on bleomycin-induced pulmonary fibrosis in rats.
Idiopathic pulmonary fibrosis is the most prevalent chronic fibrosing lung disease. Peroxisome proliferator-activated receptors-gamma agonists provide potential therapy for fibrotic diseases of the lung. Peroxisome proliferator-activated receptors-alpha agonists may be helpful in the treatment of lung inflammatory diseases, however their therapeutic potential on the "fibro-proliferative" process and extracellular matrix accumulation in idiopathic pulmonary fibrosis has been less well studied. So, the present study was conducted to evaluate the anti-fibrotic effects of fenofibrate (peroxisome proliferator-activated receptors-alpha agonist) alone and in combination with rosiglitazone (peroxisome proliferator-activated receptors-gamma agonist) on lung injury induced by bleomycin administration. Oral administration of either rosiglitazone (5 mg/kg/d) or fenofibrate (100 mg/kg/d) for 14 days, attenuated the severity of bleomycin-induced lung injury and fibrosis through decreasing lung water contents, lung fibrotic grading, lung hydroxyproline contents and lung transforming growth factor-beta1 levels; with no significant difference between them. Combined low doses of rosiglitazone (1 mg/kg/d) and fenofibrate (30 mg/kg/d) provided more benefits than full separate doses of each on the deleterious effects accompanied bleomycin administration. These findings suggested the potential use of peroxisome proliferator-activated receptors-alpha ligands as anti-fibrotic agents in lung fibrosis. Additionally, the concurrent administration of fenofibrate and rosiglitazone in low doses has synergistic effect and enhanced the beneficial effects afforded by either fenofibrate or rosiglitazone.
Department of Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt.
M
M
Samah
Abd El-Rahman
Ael-R
El-Aidy
Mona K
MK
Tawfik
Mohamed M S
MM
Ewais
D000818:Animals; D000933:Antifibrinolytic Agents / Q000008:administration & dosage*; D001761:Bleomycin / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004359:Drug Therapy, Combination; D011345:Fenofibrate / Q000008:administration & dosage*; D008297:Male; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage*; D016896:Treatment Outcome
D000933:Antifibrinolytic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D001761:Bleomycin; D011345:Fenofibrate