title: Atorvastatin attenuates the paraquat-induced pulmonary inflammation via PPARγ receptors: a new indication for atorvastatin.
abstract: This study was carried out to highlight the role of PPARγ receptors and atorvastatin's protective effect on paraquat (PQ)-induced inflammation in the lungs. Forty-two male Wistar rats were exposed either against saline as control or PQ (3.5 mg/kg, IP) as test groups for 14 days. The test groups were nominated as: PQ, pioglitazone (PGT, 10 mg/kg, orally), atorvastatin (STN, 10 mg/kg, orally), PGT+STN, PGT+GW9662 (1 mg/kg) and STN+GW9662 (1 mg/kg). PGT and STN significantly (P<0.05) reduced the PQ-elevated myeloperoxidase activity, nitric oxide and malondialdehyde contents of the lungs and IL-6 and TNF-α concentrations in serum. Histopathological studies revealed alveolar edema and hemorrhages along with hyaline exudates in alveoli confirming that PGT and STN reduced the damages. Immunohistochemistry studies showed that the PQ-induced inflammation resulted in a severe recruitment of CD68(+) macrophages, which PGT and STN remarkably diminished them. STN regulated the PQ-up-regulated COX-2 expression. The antagonistic effect of GW9662 as an absolute antagonist of PPARγ receptors on anti-inflammatory effect of STN in the regulation of COX-2 expression was observed. These data provide a molecular proof(s) of the STN-produced protective effects on the PQ-induced pulmonary inflammation, which is antagonized by PPARγ antagonist indicating its anti-inflammatory effects via PPARγ receptors. Moreover, a new indication for atorvastatin is suggested.
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran. Electronic address: hassanmalekinejad@yahoo.com.
authors.forename: Hassan
authors.initials: H
authors.lastname: Malekinejad
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.
authors.forename: Mona
authors.initials: M
authors.lastname: Khoramjouy
authors.affiliation: Department of Pathology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.
authors.forename: Rahim
authors.initials: R
authors.lastname: Hobbenaghi
authors.affiliation: Department of Pathology, Islamic Azad University, Urmia Branch, Urmia, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Amniattalab
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000069059:Atorvastatin; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use; D006540:Herbicides; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D010269:Paraquat; D009195:Peroxidase / Q000378:metabolism; D000077205:Pioglitazone; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use; D017208:Rats, Wistar; D045162:Thiazolidinediones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D006538:Heptanoic Acids; D006540:Herbicides; D015850:Interleukin-6; D047495:PPAR gamma; D011758:Pyrroles; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D008315:Malondialdehyde; D000069059:Atorvastatin; D009195:Peroxidase; D010269:Paraquat; D000077205:Pioglitazone
keywords: Antagonist; Combination therapy; Cyclooxygenase-2; Paraquat; Pro-inflammatory cytokine