{"title":"抗坏血酸加剧铁毒性对肠道屏障功能对沙门氏菌感染。","authors":"Tengjiao Guo, Yisheng Yang, Jiayou Zhang, Yu Miao, Feifei Lin, Suqin Zhu, Caili Zhang, Haohao Wu","doi":"10.1080/26896583.2020.1729632","DOIUrl":null,"url":null,"abstract":"<p><p>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 <i>Salmonella enterica</i> serovar <i>Typhimurium</i>. 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 <i>Salmonella</i>-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 <i>Salmonella</i> infection through pro-oxidant impairment of intestinal epithelial barrier from extracellular side and/or by facilitating intestinal pathogen colonization.</p>","PeriodicalId":53200,"journal":{"name":"Journal of Environmental Science and Health Part C-Toxicology and Carcinogenesis","volume":"38 1","pages":"91-107"},"PeriodicalIF":1.2000,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/26896583.2020.1729632","citationCount":"2","resultStr":"{\"title\":\"Ascorbate exacerbates iron toxicity on intestinal barrier function against <i>Salmonella</i> infection.\",\"authors\":\"Tengjiao Guo, Yisheng Yang, Jiayou Zhang, Yu Miao, Feifei Lin, Suqin Zhu, Caili Zhang, Haohao Wu\",\"doi\":\"10.1080/26896583.2020.1729632\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 <i>Salmonella enterica</i> serovar <i>Typhimurium</i>. 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 <i>Salmonella</i>-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 <i>Salmonella</i> infection through pro-oxidant impairment of intestinal epithelial barrier from extracellular side and/or by facilitating intestinal pathogen colonization.</p>\",\"PeriodicalId\":53200,\"journal\":{\"name\":\"Journal of Environmental Science and Health Part C-Toxicology and Carcinogenesis\",\"volume\":\"38 1\",\"pages\":\"91-107\"},\"PeriodicalIF\":1.2000,\"publicationDate\":\"2020-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1080/26896583.2020.1729632\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Environmental Science and Health Part C-Toxicology and Carcinogenesis\",\"FirstCategoryId\":\"93\",\"ListUrlMain\":\"https://doi.org/10.1080/26896583.2020.1729632\",\"RegionNum\":4,\"RegionCategory\":\"环境科学与生态学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2020/4/27 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"ENVIRONMENTAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Environmental Science and Health Part C-Toxicology and Carcinogenesis","FirstCategoryId":"93","ListUrlMain":"https://doi.org/10.1080/26896583.2020.1729632","RegionNum":4,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2020/4/27 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}
Ascorbate exacerbates iron toxicity on intestinal barrier function against Salmonella infection.
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.