Park Seong-Hwan, Kim Juil, Kim Dongwook, Moon Yuseok
Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Pusan National University School of Medicine, Yangsan, South Korea; Research Institute for Basic Sciences and Medical Research Institute, Pusan National University, Busan, South Korea; Immunoregulatory Therapeutics Group, Brain Busan 21 Project, Busan, South Korea.
Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Pusan National University School of Medicine, Yangsan, South Korea; Immunoregulatory Therapeutics Group, Brain Busan 21 Project, Busan, South Korea.
Toxicol In Vitro. 2017 Feb;38:108-116. doi: 10.1016/j.tiv.2016.10.003. Epub 2016 Oct 11.
Deoxynivalenol (DON), the most prevalent mycotoxin worldwide, leads to economic losses for animal food production. Swine is a most sensitive domestic animal to DON due to rapid absorption and low detoxification by gut microbiota. Specifically, DON can severely damage pig intestinal tissue by disrupting the intestinal barrier and inducing inflammatory responses. We evaluated the effects of several mycotoxin detoxifiers including bentonites, yeast cell wall components, and mixture-typed detoxifier composed of mineral, microorganisms, and phytogenic substances on DON-insulted intestinal barrier and pro-inflammatory responses using in vitro porcine enterocyte culture model. DON-induced disruption of the in vitro gut barrier was attenuated by all three mycotoxin detoxifiers in dose-dependent manners. These mycotoxin detoxifiers also suppressed DON-induced pro-inflammatory chemokine expression to different degrees, which was mediated by downregulation of mitogen-activated kinases and early growth response-1. Of note, the mixture-typed detoxifier was the most prominent mitigating agent at the cellular levels whereas the high dose of bentonite clay also had suppressive action against DON-induced pro-inflammatory insult. The in vitro porcine enterocyte-based assessment of intestinal barrier integrity and inflammatory signals provides sensitive and simplified alternative bioassay of feed additives such as detoxifiers against enteropathogenic mycotoxins with comprehensive mechanistic confirmation.
脱氧雪腐镰刀菌烯醇(DON)是全球最普遍的霉菌毒素,会给动物食品生产造成经济损失。猪是对DON最敏感的家畜,因为其吸收迅速且肠道微生物群的解毒能力较低。具体而言,DON可通过破坏肠道屏障和引发炎症反应严重损害猪的肠道组织。我们使用体外猪肠上皮细胞培养模型,评估了几种霉菌毒素解毒剂,包括膨润土、酵母细胞壁成分以及由矿物质、微生物和植物源物质组成的混合型解毒剂,对受DON损伤的肠道屏障和促炎反应的影响。所有三种霉菌毒素解毒剂均以剂量依赖的方式减轻了DON诱导的体外肠道屏障破坏。这些霉菌毒素解毒剂还不同程度地抑制了DON诱导的促炎趋化因子表达,这是由丝裂原活化蛋白激酶和早期生长反应-1的下调介导的。值得注意的是,在细胞水平上,混合型解毒剂是最显著的缓解剂,而高剂量的膨润土对DON诱导的促炎损伤也有抑制作用。基于体外猪肠上皮细胞对肠道屏障完整性和炎症信号的评估,为饲料添加剂(如针对肠道致病性霉菌毒素的解毒剂)提供了敏感且简化的替代生物测定方法,并具有全面的作用机制验证。