Ascorbic acid is often used to enhance iron absorption in nutritional interventions, but it produces pro-oxidant effects in the presence of iron. This study aimed to evaluate ascorbate's role in iron toxicity on intestinal resistance against foodborne pathogens during iron supplementation/fortification. In polarized Caco-2 cell monolayers, compared to the iron-alone treatment, the iron-ascorbate co-treatment caused more than 2-fold increase in adhesion, invasion and translocation of Salmonella enterica serovar Typhimurium. According to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, lactate dehydrogenase release and transepithelial electrical resistance, the iron-ascorbate co-treatment resulted in reduced cell viability and increased impairment of cell membrane and paracellular permeability compared to the iron-alone treatment. Butylated hydroxytoluene protected cells against these prooxidant toxicities of ascorbate. Ascorbate completely restored iron-induced intracellular oxidant burst and depletion of cytosolic antioxidant reserve, according to dichlorodihydrofluorescein fluorescence and intracellular reduced glutathione levels. In Salmonella-infected C57BL/6 mice, iron-ascorbate co-supplementation resulted in greater loss of body weight and appetite, lower survival rate, shorter colon length, heavier intestinal microvilli damage, and more intestinal pathogen colonization and translocation than the iron-alone supplementation. Overall, ascorbate would exacerbate iron toxicity on intestinal resistance against Salmonella infection through pro-oxidant impairment of intestinal epithelial barrier from extracellular side and/or by facilitating intestinal pathogen colonization.

中文翻译：

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抗坏血酸会加剧铁对沙门氏菌感染的肠道屏障功能的毒性。

在营养干预中，抗坏血酸通常用于增强铁的吸收，但在铁的存在下它会产生促氧化作用。本研究旨在评估抗坏血酸在铁补充/强化期间对肠道对食源性病原体的抵抗力方面的铁毒性作用。在极化的 Caco-2 细胞单层中，与单独铁处理相比，铁-抗坏血酸联合处理导致肠道沙门氏菌鼠伤寒沙门氏菌的粘附、侵袭和易位增加了 2 倍以上。根据3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑测定，乳酸脱氢酶释放和跨上皮电阻，与单独铁处理相比，抗坏血酸铁联合处理导致细胞活力降低，细胞膜和细胞旁通透性受损增加。丁基化羟基甲苯保护细胞免受抗坏血酸的这些促氧化毒性。根据二氯二氢荧光素荧光和细胞内还原型谷胱甘肽水平，抗坏血酸完全恢复了铁诱导的细胞内氧化剂爆发和细胞溶质抗氧化剂储备的消耗。在感染沙门氏菌的 C57BL/6 小鼠中，与单独铁相比，抗坏血酸铁联合补充剂导致体重和食欲的更大损失、更低的存活率、更短的结肠长度、更严重的肠道微绒毛损伤以及更多的肠道病原体定植和易位补充。总体，