title: Antifibrotic effect of atorvastatin on paraquat-induced pulmonary fibrosis: role of PPARγ receptors.
abstract: This study was carried out to highlight the role of PPARγ in the paraquat (PQ)-induced pulmonary fibrosis. Forty-two male Wistar rats were exposed either against saline as a control group or PQ (3.5mg/kg, i.p.) as test groups. The test groups were nominated as PQ (PQ-exposed non-treated animals), pioglitazone (PGT, 10mg/kg, orally), atorvastatin (STN, 10mg/kg, orally), PGT+STN, PGT+GW9662 (1mg/kg, i.p.) and STN+GW9662 (1mg/kg). Atorvastatin but not PGT was able to reverse significantly (P<0.05) the PQ-increased ratio of lung to body weight. STN was successfully able to recover the PQ-reduced antioxidant potency and the GW9662 administration resulted in antagonizing the protective effect of both PGT and STN. Although both PGT and STN were able to reduce the hydrxoproline content of the lungs, GW9662, however, could reverse only STN-related effect. Histochemical studies revealed that PQ exposure resulted in a remarkable increase of fibroblasts and collagen fibers in the interstitial tissue and around vessels and bronchioles, which was improved by the STN administration. Only STN-received animals showed the down-regulation of the TGF-β1 expression and GW9662 was able to antagonize this down-regulation. Co-administration of PGT and STN could not exert any synergistic protective effect. These data suggest that the PQ-induced pulmonary fibrosis could be more effectively reversed by STN rather than PGT. Moreover, STN-induced protective effects might attribute to the regulation of TGF-β1 expression, which is antagonized by PPARγ antagonist, suggesting that STN may improve the PQ-induced damages via PPARγ.
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Veterinary Medicine, P.O. Box 1177, Urmia University, Urmia, Iran. Electronic address: hassanmalekinejad@yahoo.com.
authors.forename: Hassan
authors.initials: H
authors.lastname: Malekinejad
authors.forename: Masoud
authors.initials: M
authors.lastname: Mehrabi
authors.forename: Mona
authors.initials: M
authors.lastname: Khoramjouy
authors.forename: Ali
authors.initials: A
authors.lastname: Rezaei-Golmisheh
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D000069059:Atorvastatin; D001835:Body Weight / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D006540:Herbicides; D006909:Hydroxyproline / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D047495:PPAR gamma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010269:Paraquat; D000077205:Pioglitazone; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D045162:Thiazolidinediones / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000235:genetics
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D006538:Heptanoic Acids; D006540:Herbicides; D047495:PPAR gamma; D020011:Protective Agents; D011758:Pyrroles; D012333:RNA, Messenger; D045162:Thiazolidinediones; D053773:Transforming Growth Factor beta1; D000069059:Atorvastatin; D010269:Paraquat; D006909:Hydroxyproline; D000077205:Pioglitazone
keywords: Antagonist; Hydroxyproline; Peroxisome proliferator-activated receptor; Pulmonary fibrosis; Transforming growth factor-β1