Journal
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
Volume 114, Issue -, Pages 79-89Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.pestbp.2014.06.011
Keywords
Antagonist; Combination therapy; Cyclooxygenase-2; Paraquat; Pro-inflammatory cytokine
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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. (C) 2014 Elsevier Inc. All rights reserved.
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