Abstract
The effects of Zataria multiflora (Z. multiflora) and pioglitazone (a PPAR-γ agonist) alone and in combination, on systemic inflammation and oxidative stress induced by inhaled paraquat (PQ) as a herbicide, which induced inflammation in rats, were examined. Rats were exposed to (1) saline (control) and (2) 54 mg/m3 PQ aerosols (8 times, every other day, each time for 30 min) without treatment or treated with (3 and 4) two doses of Z. multiflora (200 and 800 mg/kg/day), (5 and 6) two doses of pioglitazone (5 and 10 mg/kg/day), (7) low doses of Z.multiflora + pioglitazone, (Pio-5+Z-200 mg/kg/day) or (8) dexamethasone (0.03 mg/kg/day) for 16 days, after the last PQ exposure. Different variables were measured at the end of the treatment period. Exposure to PQ significantly increased total and differential white blood cells (WBC) counts, serum levels of nitrite (NO2), malondialdehyde (MDA), interleukin- (IL) 17, and tumor necrosis factor alpha (TNF-α), but reduced thiol, superoxide dismutase (SOD), catalase (CAT), IL-10, and interferon-gamma (INF-γ) (p < 0.05 to p < 0.001). Most measured parameters were significantly improved in groups treated with either doses of the extract, pioglitazone, Pio-5+Z-200 mg/kg/day, or dexamethasone compared to the PQ group (p < 0.05 to p < 0.001). The combination of low doses of Pio-5+Z-200 mg/kg/day showed significantly higher effects compared to each one alone (p < 0.05 to p < 0.001). Systemic oxidative stress and inflammation due to inhaled PQ were improved by Z. multiflora and pioglitazone. Higher effects of Pio-5+Z-200 mg/kg/day compared to each one alone suggest modulation of PPAR-γ receptors by the plant extract, but further studies using PPAR-γ antagonists need to be done in this regard.
Highlights
Paraquat (PQ) (C12 H14 N2), a bipyridinium and nonselective quaternary nitrogen herbicide, is commonly used worldwide [1]
Eight groups of rats (n = 6 in each group) were studied: (1) control group, which was exposed to normal saline aerosol; (2) animals exposed to PQ (Sigma-Aldrich Co., China) aerosol at dose of 54 mg/m3 [13,14,15]; (3 and 4) two groups exposed to PQ 54 mg/m3 and treated with two doses of the extract of Z. multiflora (200 and 800 mg/kg/day); (5 and 6) two groups exposed to PQ 54 mg/m3 and treated with two doses (5 and 10 mg/kg/day) of the pioglitazone (Samisaz Pharmaceutical Company, Iran); (7) one group exposed to PQ 54 mg/m3 and treated with Pio-5+Z-200 mg/kg/day; and (8) one group exposed to PQ 54 mg/m3 and treated with dexamethasone
Total and differential white blood cells (WBC) were increased in the blood of animals exposed to inhaled PQ compared to the control group (p < 0:05 for lymphocytes and p < 0:001 for other cases)
Summary
Paraquat (PQ) (C12 H14 N2), a bipyridinium and nonselective quaternary nitrogen herbicide, is commonly used worldwide [1]. In 1985, only in Japan, approximately 2000 deaths occurred/year due to PQ digestion which were mostly intentional, and in 2020, more than 150,000 people died due to pesticide poisoning [2, 3]. PQ intoxication is characterized by swelling, bleeding, inflammation, and proliferation of bronchial epithelial cells [4]. Sacrificing and measurements or intentional in humans and animals, and the most common routes of exposure are inhalation and dermal [5]. PQ causes burning and swelling of the mouth and throat, followed by gastrointestinal symptoms such as abdominal pain, loss of appetite, nausea, vomiting, diarrhea, and systemic inflammation [6]. It has been reported that administration of PQ can lead to an increase in inflammatory factors such as TNF-α [7]
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