Liao Chengshui, Xu Fengru, Yu Zuhua, Ding Ke, Jia Yanyan
Laboratory of Functional Microbiology and Animal Health, College of Animal Science and Technology, Henan University of Science and Technology, Luoyang 471023, China.
Luoyang Key Laboratory of Live Carrier Biomaterial and Animal Disease Prevention and Control, Luoyang 471023, China.
Vet Sci. 2024 Jun 28;11(7):291. doi: 10.3390/vetsci11070291.
Mycotoxins are secondary metabolites produced by several fungi and moulds that exert toxicological effects on animals including immunotoxicity, genotoxicity, hepatotoxicity, teratogenicity, and neurotoxicity. However, the toxicological mechanisms of mycotoxins are complex and unclear. The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome is a multimeric cytosolic protein complex composed of the NLRP3 sensor, ASC adapter protein, and caspase-1 effector. Activation of the NLRP3 inflammasome plays a crucial role in innate immune defence and homeostatic maintenance. Recent studies have revealed that NLRP3 inflammasome activation is linked to tissue damage and inflammation induced by mycotoxin exposure. Thus, this review summarises the latest advancements in research on the roles of NLRP3 inflammasome activation in the pathogenesis of mycotoxin exposure. The effects of exposure to multiple mycotoxins, including deoxynivalenol, aflatoxin B1, zearalenone, T-2 toxin, ochratoxin A, and fumonisim B1, on pyroptosis-related factors and inflammation-related factors in vitro and in vivo and the pharmacological inhibition of specific and nonspecific NLRP3 inhibitors are summarized and examined. This comprehensive review contributes to a better understanding of the role of the NLRP3 inflammasome in toxicity induced by mycotoxin exposure and provides novel insights for pharmacologically targeting NLRP3 as a novel anti-inflammatory agent against mycotoxin exposure.
霉菌毒素是由多种真菌和霉菌产生的次生代谢产物，可对动物产生毒理学影响，包括免疫毒性、遗传毒性、肝毒性、致畸性和神经毒性。然而，霉菌毒素的毒理学机制复杂且尚不清楚。含核苷酸结合寡聚化结构域（NOD）样受体（NLR）家族pyrin结构域3（NLRP3）炎性小体是一种多聚体胞质蛋白复合物，由NLRP3传感器、ASC衔接蛋白和caspase-1效应器组成。NLRP3炎性小体的激活在先天免疫防御和稳态维持中起关键作用。最近的研究表明，NLRP3炎性小体激活与霉菌毒素暴露诱导的组织损伤和炎症有关。因此，本综述总结了NLRP3炎性小体激活在霉菌毒素暴露发病机制中的作用的最新研究进展。总结并研究了暴露于多种霉菌毒素，包括脱氧雪腐镰刀菌烯醇、黄曲霉毒素B1、玉米赤霉烯酮、T-2毒素、赭曲霉毒素A和伏马菌素B1，对体外和体内焦亡相关因子和炎症相关因子的影响以及特异性和非特异性NLRP3抑制剂的药理抑制作用。这篇全面的综述有助于更好地理解NLRP3炎性小体在霉菌毒素暴露诱导的毒性中的作用，并为将NLRP3作为一种新型的抗霉菌毒素暴露的抗炎剂进行药理靶向提供新的见解。
