Carvacrol and Zataria multiflora influenced the PPARγ agonist effects on systemic inflammation and oxidative stress induced by inhaled paraquat in rat

Objectives: The effects of PPAR-γ agonist alone and in combination with carvacrol and Zataria multiflora on inhaled paraquat (PQ) induced-systemic inflammation and oxidative stress were examined.

Materials and methods: Control group exposed to normal saline aerosol, one group exposed to 54 mg/m³ PQ aerosol and four groups exposed to PQ aerosol and treated with 5 mg/kg/day pioglitazone, pioglitazone + 200 mg/kg/day Z. multiflora extract, pioglitazone + 20 mg/kg/day carvacrol, and 0.03 mg /kg/day dexamethasone for 16 days after the end of exposure to PQ were studied. Exposure to normal saline or PQ was performed every other days for 30 min (8 times). Different variables were measured after the end of treatment period.

Results: PQ exposure significantly increased serum levels of NO₂, MDA and IL-6 but dexreased CAT and IFN-γ levels and IFN-γ/IL-6 ratio compared to control group (P<0.01 to P<0.001). Treatment with pioglitazone only improved serum level of MDA (P<0.01). Treatment with combination of pioglitazone and carvacrol as well as treatment with dexamethasone improved all measured variables compared to PQ exposed group (P<0.05 to P<0.001). The effects of pioglitazone + Z. multiflura and pioglitazone + carvacrol on almost all measured variables were significantly higher than pioglitazone alone (P<0.05 to P<0.001).

Conclusion: The effects of combination therapy of pioglitazone with Z. multiflora or carvacrol on inhaled paraquat (PQ) induced-oxidative stress and systemic inflammation were higher than the effects of pioglitazone alone. These results suggested that the effects of the extract and carvacrol may mediated through PPAR-γ receptors.

Keywords: Carvacrol; Oxidative stress; PPAR-γ agonist; Paraquat; Systemic inflammation; Zataria multiflora.