College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, P. R. China.
Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, Harbin, 150030, P. R. China.
Food Funct. 2022 Mar 21;13(6):3551-3560. doi: 10.1039/d1fo02857j.
Nlrp3 is a vital integration point of diverse extracellular stimuli and cellular stress. However, the inappropriate activation of Nlrp3 results in the progression of autoinflammatory and metabolic disorders. Atrazine, which is used widely in the agricultural sector, is toxic to humans. Herein, this study found that atrazine could induce oxidative stress and the expression of Nfkb and IRF1 in spleen, promoting the ox-mtDNA formation. Also, production and release of ox-mtDNA stimulated the Nlrp3 inflammasome. Lastly, atrazine induced pyroptosis in spleen, mediating the activation of Nlrp3 inflammasome. In addition, lycopene, a kind of carotenoid, is natural bioactive component in fruits and vegetables, which is applied toward reducing oxidative stress. It was found that lycopene could ameliorate the pyroptosis induced by atrazine the inhibition of ox-mtDNA production. The results also provided evidence that lycopene had a potential role in the prevention of Nlrp3 inflammasome activation by depleting the ox-mtDNA.
Nlrp3 是多种细胞外刺激和细胞应激的重要整合点。然而，Nlrp3 的异常激活会导致自身炎症和代谢紊乱的进展。阿特拉津是农业领域广泛使用的一种物质，对人类具有毒性。本研究发现，阿特拉津可诱导脾脏氧化应激和 Nfkb 和 IRF1 的表达，促进 ox-mtDNA 的形成。此外，ox-mtDNA 的产生和释放可刺激 Nlrp3 炎性小体。最后，阿特拉津诱导脾脏发生细胞焦亡，介导 Nlrp3 炎性小体的激活。此外，番茄红素是一种类胡萝卜素，是水果和蔬菜中的天然生物活性成分，可用于减轻氧化应激。研究发现，番茄红素可通过抑制 ox-mtDNA 的产生来改善阿特拉津诱导的细胞焦亡。这些结果还提供了证据表明，番茄红素通过耗竭 ox-mtDNA 而具有抑制 Nlrp3 炎性小体激活的潜力。
