Atorvastatin attenuates the paraquat-induced pulmonary inflammation via PPAR gamma receptors: A new indication for atorvastatin

作者：Malekinejad Hassan^*; Khoramjouy Mona; Hobbenaghi Rahim; Amniattalab Amir

来源：Pesticide Biochemistry and Physiology, 2014, 114: 79-89.

DOI：10.1016/j.pestbp.2014.06.011

• Antagonist
• Combination therapy
• Cyclooxygenase-2
• Paraquat
• Pro-inflammatory cytokine

This study was carried out to highlight the role of PPAR gamma 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-alpha 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 PPAR gamma 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 PPAR gamma antagonist indicating its anti-inflammatory effects via PPAR gamma receptors. Moreover, a new indication for atorvastatin is suggested.

• 出版日期2014-9