Jamshidi Vahid, Halabian Raheleh, Saeedi Pardis, Bagheri Hasan, Nobakht Motlagh Ghoochani Bibi Fatemeh
Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran 14359-44711, Iran.
Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran 14359-44711, Iran.
Toxicol Res (Camb). 2023 Apr 17;12(3):369-380. doi: 10.1093/toxres/tfad016. eCollection 2023 Jun.
Chemical warfare victims suffer from bronchiolitis and chronic pulmonary obstruction caused by sulfur mustard (SM) toxicity. Despite the mesenchymal stem cells capacity to alleviate inflammation, their low survival rate under oxidative stress severely limits their effectiveness. This study aimed to examine how natural (Crocin) and synthetic (Dexamethasone) antioxidants might affect MSC efficacy. MSCs were treated with the optimal doses of Crocin (Cr.), Dexamethasone (Dex.), and their combination. The A549 cells line was pretreated with the optimal dose of the CEES to mimic the lung disease. Then, the affected A549 cells were exposed to the preconditioned MSCs and conditioned media, and then their survival rates were estimated by MTTor2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Annexin-V PI apoptosis test was conducted for MSCs and A549 cells. Reactive Oxygen Species (ROS) assay and Enzyme-linked immunosorbent assay (ELISA) test demonstrated the percentage of production of ROS and the cytokines levels in A549/CEES, respectively. The results revealed significant increases in Cr. + Dex. treated MSCs ( < .01) and A549 cells treated with MSCs-CM/Cr/Dex ( < .01) groups' survival. The apoptosis rate and ROS production were reduced in the MSCs-CM/Cr/Dex. Also, considerable decreases in IL-1β ( < .01) and IL-6 ( < .01) and a significant increase in IL-10 ( < .05) in treated A549/CEES by Cr/Dex and MSCs-CM/Cr/Dex supported the synergistic effects of Crocin and Dexamethasone.
化学战受害者会遭受由芥子气（SM）毒性引起的细支气管炎和慢性肺阻塞。尽管间充质干细胞有减轻炎症的能力，但其在氧化应激下的低存活率严重限制了它们的有效性。本研究旨在探究天然抗氧化剂（藏红花素）和合成抗氧化剂（地塞米松）如何影响间充质干细胞的功效。用藏红花素（Cr.）、地塞米松（Dex.）的最佳剂量及其组合处理间充质干细胞。用最佳剂量的2-氯乙基乙基硫醚（CEES）预处理A549细胞系以模拟肺部疾病。然后，将受影响的A549细胞暴露于预处理的间充质干细胞和条件培养基中，然后通过MTT（噻唑蓝）或2,5-二苯基-2H-四唑溴盐（MTT）测定法评估其存活率。对间充质干细胞和A549细胞进行膜联蛋白-V碘化丙啶凋亡检测。活性氧（ROS）测定和酶联免疫吸附测定（ELISA）试验分别显示了A549/CEES中ROS的产生百分比和细胞因子水平。结果显示，Cr. + Dex.处理的间充质干细胞组（P <.01）以及用间充质干细胞条件培养基/Cr/Dex处理的A549细胞组（P <.01）的存活率显著提高。间充质干细胞条件培养基/Cr/Dex组的凋亡率和ROS产生减少。此外，Cr/Dex和间充质干细胞条件培养基/Cr/Dex处理的A549/CEES中白细胞介素-1β（IL-1β，P <.01）和白细胞介素-6（IL-6，P <.01）显著降低，白细胞介素-10（IL-10，P <.05）显著升高，这支持了藏红花素和地塞米松的协同作用。
