Atorvastatin attenuates the paraquat-induced pulmonary inflammation via PPARγ receptors: a new indication for atorvastatin.

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.