Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Toxicon. 2023 Nov;235:107316. doi: 10.1016/j.toxicon.2023.107316. Epub 2023 Oct 10.
Paraquat is a green liquid toxin that is used in agriculture and can induce multi-organ including lung injury. Various pharmacological effects of Crocus sativus (C. sativus) were indicated in previous studies. In this research, the effects of C. sativus extract and pioglitazone on inhaled paraquat-induced lung inflammation, oxidative stress, pathological changes, and tracheal responsiveness were studied in rats. Eight groups of rats (n = 7 in each) including control (Ctrl), untreated paraquat aerosol exposed group (54 mg/m, 8 times in alternate days), paraquat treated groups with dexamethasone (0.03 mg/kg/day, Dexa) as positive control, two doses of C. sativus extract (20 and 80 mg/kg/day, CS-20 and CS-80), pioglitazone (5 and 10 mg/kg/day, Pio-5 and Pio-10), and the combination of CS-20 + Pio-5 were studied. Total and differential WBC, levels of oxidant and antioxidant biomarkers in the BALF, lung tissue cytokine levels, tracheal responsiveness (TR), and pathological changes were measured. The levels of IFN-γ, IL-10, SOD, CAT, thiol, and EC were reduced, but MDA level, total and differential WBC count in the BALF and lung pathological changes were increased in the paraquat group (all, p < 0.001). The levels of IFN-γ, IL-10, SOD, CAT, thiol and EC were increased but BALF MDA level, lung pathological changes, total and differential WBC counts were reduced in all treated groups. The effects of C. sativus high dose and combination groups on measured parameters were equal or even higher than dexamethasone (p < 0.05 to p < 0.001). The effects of the combination of CS-20 + Pio-5 on most variables were significantly higher than CS-20 and Pio-5 alone (p < 0.05 to p < 0.001). C. sativus treatment improved inhaled paraquat-induced lung injury similar to dexamethasone and showed a synergistic effect with pioglitazone, suggesting possible PPAR-γ receptor-mediated effects of the plant.
百草枯是一种绿色液体毒素，用于农业，并可导致包括肺损伤在内的多种器官损伤。先前的研究表明，藏红花（Crocus sativus，C. sativus）具有多种药理学作用。在这项研究中，研究了藏红花提取物和吡格列酮对吸入百草枯诱导的肺炎症、氧化应激、病理变化和气管反应性的影响。将 8 组大鼠（每组 7 只）分为对照组（Ctrl）、未处理的百草枯气雾剂暴露组（54mg/m，8 次，隔日）、地塞米松（0.03mg/kg/天，Dexa）作为阳性对照组、两个剂量的藏红花提取物（20 和 80mg/kg/天，CS-20 和 CS-80）、吡格列酮（5 和 10mg/kg/天，Pio-5 和 Pio-10）以及 CS-20+Pio-5 联合组。测量 BALF 中的总白细胞和分类白细胞、氧化和抗氧化生物标志物水平、肺组织细胞因子水平、气管反应性（TR）和病理变化。百草枯组的 IFN-γ、IL-10、SOD、CAT、硫醇和 EC 水平降低，但 BALF 中的 MDA 水平、总白细胞和分类白细胞计数以及肺病理变化增加（均 p<0.001）。所有治疗组的 IFN-γ、IL-10、SOD、CAT、硫醇和 EC 水平均升高，但 BALF MDA 水平、肺病理变化、总白细胞和分类白细胞计数均降低。藏红花高剂量组和联合组对测量参数的影响与地塞米松相当或甚至更高（p<0.05 至 p<0.001）。CS-20+Pio-5 联合组对大多数变量的影响明显高于 CS-20 和 Pio-5 单独组（p<0.05 至 p<0.001）。藏红花治疗可改善吸入百草枯引起的肺损伤，与地塞米松相似，并与吡格列酮表现出协同作用，提示该植物可能通过过氧化物酶体增殖物激活受体-γ 受体发挥作用。
