Control rats were exposed to saline aerosol, two groups were exposed to paraquat (PQ), 27 (PQ-L) and 54 (PQ-H) mg/m 3 aerosols and six groups were treated with carvacrol, 20 (C-L) and 80 (C-H) mg/kg/day, pioglitazone, 5 (Pio-L) and 10 (Pio-H) mg/kg/day, C-L+Pio-L and dexamethasone, 0.03 mg/kg/day, for 16 days after the end of exposure to PQ-H. Different variables were measured after the end of treatment period. Total and differential white blood cells counts, nitrite, malondialdehyde, interleukin (IL)-10, and interferon-gamma levels were significant increased, but thiol, superoxide dismutase, catalase, IL-17, and tumor necrosis factor alpha were decreased in the blood due to both doses of PQ (p < 0.05-p < 0.001). Most measured parameters were significantly improved in treated groups with both doses of carvacrol, pioglitazone, the combination of C-L+Pio-L and dexamethasone compared to PQ-H group (p < 0.05-p < 0.001).

Exposed rats to normal saline and paraquat (PQ) aerosol as control and PQ group, rats exposed to PQ and treated with 20 and 80 mg/kg/day carvacrol, 5 and 10 mg/kg/day pioglitazone, low dose of pioglitazone + carvacrol and 0.03 mg/kg/day dexamethasone (Dexa) for 16 days after the end of PQ exposure were studied (n = 6 in each group). Lung pathological changes, tracheal responsiveness to methacholine and ovalbumin (OVA) as well as transforming growth factor beta (TGF-β) and interleukin (IL)-6 level in the lung tissue homogenize as well as TGF-β, IL-6, oxidant and antioxidant levels oxidant and antioxidants were increased in PQ group (p < 0.01 to p < 0.001). Lung pathological changes, tracheal responsiveness to methacholine and OVA as well as TGF-β, IL-6 oxidant and antioxidant levels were improved in all treated groups except lung pathological changes in treated group with low dose of pioglitazone (p < 0.05 to p < 0.001). The effects of low dose of pioglitazone and carvacrol alone were significantly lower than in the combination group of low dose of pioglitazone + carvacrol (p < 0.05 to p < 0.001). Carvacrol treatment improved inhaled PQ-induced lug injury similar to the effects of dexamethasone. The synergic effect of carvacrol and pioglitazone suggests PPAR-γ receptor mediated effects of carvacrol on inhaled PQ-induced lung injury.

Urginea maritima (U. maritima) showed anti-inflammatory, antioxidant, antibacterial, diuretic, vasodilatation, and wound-healing effects on fungal infections, cardiac disorders, digestive disorders, rheumatoid disease, and respiratory disorders such as bronchitis, bronchial nosocomial infections, and severe cough. To examine the bronchodilatory effect of U. maritima, the relaxant effect of its extract on rat tracheal smooth muscle (TSM) and its possible mechanism was examined in this study. Male Wistar rats’ TSM were divided into eight groups (n = 8 in each group). Four of these groups were TSM tissues, contracted with KCl (60 mM) incubated with atropine, glibenclamide, and indomethacin and nonincubated TSM, while the other four groups were TSM tissues contracted with methacholine (10 μM) for 5 min, incubated with propranolol, chlorpheniramine, and diltiazem and nonincubated TSM. Cumulative concentrations of U. maritima extract (12.5, 25, 50, 100, 20, and 400 μg/ml) were then added to organ bath every 5 min. Theophylline (0.2, 0.4, 0.6, and 0.8 mM) as positive control and saline (1 ml) as negative control were also examined in nonincubated tissues. A concentration-dependent relaxant effect of U. maritima on nonincubated TSM contracted with KCl (60 mM) or methacholine (10 μM) ( p < 0.01 and p < 0.001 ) was observed. The relaxant effects of U. maritima extract in the incubated tissues with glibenclamide, propranolol, diltiazem, atropine, and chlorpheniramine were significantly lower than those in the nonincubated tissues ( p < 0.05 to p < 0.001 ). EC50 values of U. maritima extract in the incubated TSM with glibenclamide, propranolol, diltiazem, and atropine were significantly higher than those in the nonincubated tissues ( p < 0.05 for diltiazem-incubated tissues and p < 0.001 for other cases). U. maritima extract displayed considerable relaxant effect on TSM comparable to the effect of theophylline. Beta-2 adrenoceptor stimulation and muscarinic receptor inhibition as well as potassium opening and calcium channels blocking effects are the possible mechanisms for the relaxant effects of the plant.

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The effects of a PPAR-γ agonist, pioglitazone and Zataria multiflora (Z. multiflora) on inhaled paraquat (PQ)-induced lung oxidative stress, inflammation, pathological changes and tracheal responsiveness were examined. The study was carried out in control rats exposed to normal aerosol of saline, PQl and PQh groups exposed to aerosols of 27 and 54 mg/m3 PQ, groups exposed to high PQ concentration (PQh) and treated with 200 and 800 mg/kg/day Z. multiflora, 5 and 10 mg/kg/day pioglitazone, low doses of Z. multiflora + pioglitazone, and 0.03 mg/kg/day dexamethasone. Increased tracheal responsiveness, transforming growth factor beta (TGF-ß) and lung pathological changes due to PQh were significantly improved by high doses of Z. multiflora and pioglitazone, dexamethasone and extract + pioglitazone, (p < 0.05 to p < 0.001). In group treated with low doses of the extract + pioglitazone, the improvements of most measured variables were significantly higher than the low dose of two agents alone (p < 0.05 to p < 0.001). Z. multiflora improved lung injury induced by inhaled PQ similar to dexamethasone and pioglitazone which could be mediated by PPAR-γ receptor.