Institute of Infection and Immunity of Huaihe Hospital, Henan University, Kaifeng 475000, China.
School of Physical Education, Henan University, Kaifeng 475000, China.
Int Immunopharmacol. 2018 Dec;65:531-538. doi: 10.1016/j.intimp.2018.10.046. Epub 2018 Nov 6.
Paraquat (PQ) induces acute lung injury (ALI) and immunotoxicity. Apigenin exerts anti-oxidant and anti-inflammatory properties. The purpose of this study was to investigate the possible protective effects of apigenin on PQ-induced ALI and immunotoxicity in mice. Female C57BL/6 mice received a single injection of PQ (50 mg/kg). Apigenin was given for 7 consecutive days starting 5 days before PQ exposure. The toxicity markers were evaluated in terms of weight loss, lung histopathology, oxidative stress, inflammation, and T cell functions after PQ exposure. Poisoned mice exhibited severe lung tissue lesions, inflammatory cell infiltration and the release of pro-inflammatory cytokines IL-6 and TNF-α. PQ administration increased the lung wet/dry ratios and lipid peroxidation by the increase of MDA levels and decreased anti-oxidase activity including SOD, GSH-PX, and CAT. While such effect on lung was reversed by apigenin. Importantly, PQ-induced immunotoxicity was also observed in a decrease of spleen weight, inhibition of T cell proliferation and T-cell secreting IL-2 from splenocytes. Further mechanism analysis found that PQ administration could decrease total splenocytes, CD4 and CD8 T cells, SOD, GSH-PX, and CAT activity, and increased the levels of MDA and the concentrations of pro-inflammatory cytokines IL-6 and TNF-α compared to control mice. However, apigenin treatment reversed PQ-induced immunotoxicity. In summary, all results suggest that apigenin has beneficial effects on PQ-induced ALI and immunotoxicity possibly, and it could be related, at least in part, to its ability in modulating inflammation and oxidative stress, although in-depth studies might be needed to fully understand the mechanism of action.
百草枯（PQ）可诱导急性肺损伤（ALI）和免疫毒性。芹菜素具有抗氧化和抗炎作用。本研究旨在探讨芹菜素对 PQ 诱导的小鼠 ALI 和免疫毒性的可能保护作用。雌性 C57BL/6 小鼠接受单次 PQ（50mg/kg）注射。PQ 暴露前 5 天开始连续 7 天给予芹菜素。根据 PQ 暴露后体重减轻、肺组织病理学、氧化应激、炎症和 T 细胞功能评估毒性标志物。中毒小鼠表现出严重的肺组织损伤、炎症细胞浸润和促炎细胞因子 IL-6 和 TNF-α的释放。PQ 给药通过增加 MDA 水平和降低抗氧化酶活性（包括 SOD、GSH-PX 和 CAT）增加肺湿/干比和脂质过氧化。而芹菜素逆转了这种对肺的影响。重要的是，PQ 诱导的免疫毒性也表现为脾脏重量减轻、T 细胞增殖抑制和 T 细胞从脾细胞中分泌 IL-2 减少。进一步的机制分析发现，与对照组小鼠相比，PQ 给药可降低总脾细胞、CD4 和 CD8 T 细胞、SOD、GSH-PX 和 CAT 活性，增加 MDA 水平和促炎细胞因子 IL-6 和 TNF-α的浓度。然而，芹菜素治疗可逆转 PQ 诱导的免疫毒性。总之，所有结果表明，芹菜素对 PQ 诱导的 ALI 和免疫毒性具有有益作用，这可能与其调节炎症和氧化应激的能力有关，尽管需要进一步的深入研究来充分了解其作用机制。
