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首页> 外文期刊>Journal of trace elements in medicine and biology: Organ of the Society for Minerals and Trace Elements (GMS) >Oral administration of liquid iron preparation containing excess iron induces intestine and liver injury, impairs intestinal barrier function and alters the gut microbiota in rats
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Oral administration of liquid iron preparation containing excess iron induces intestine and liver injury, impairs intestinal barrier function and alters the gut microbiota in rats

机译：口服含有过量铁的液体铁制剂诱导肠道和肝损伤，损害肠道屏障功能，并在大鼠中改变肠道微生物

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The aim of this study was to determine the toxicological effects of excess iron in a liquid iron preparation (especially on intestinal barrier function) and the possible etiology of side effects or diseases caused by the excess iron. In study 1, forty male Sprague-Dawley rats (4-5 wk old) were subjected to oral gavage with 1 ml vehicle (0.01 mol/L HCl) or 1 ml liquid iron preparation containing 8 mg, 16 mg or 24 mg of iron for 30 d. Iron status, oxidative stress, histology (H&E staining), ultrastructure (electron microscopy) and apoptosis (TUNEL assay) in the intestines and liver were assessed. The cecal microbiota was evaluated by 16S rRNA sequencing. In study 2, twenty rats with the same profile as above were subjected to oral gavage with 1 ml vehicle or 24 mg Fe for 30 d. The intestinal barrier function was determined by in vivo studies and an Ussing chamber assay; tight junction proteins and serum pro-inflammatory cytokines were observed by enzyme-linked immunosorbent assay. In study 1, the intestinal mucosa and liver showed apparent oxidative stress. In addition, iron concentration-dependent ultrastructural alterations to duodenal enterocytes and hepatocytes and histological damage to the colonic mucosa were detected. Notably, apoptosis was increased in duodenal enterocytes and hepatocytes. Impaired intestinal barrier function and lower expression of intestinal tight junction proteins were observed, and the phenotype was more severe in the colon than in the duodenum. A trend toward higher expression of serum pro inflammatory cytokines might indicate systemic inflammation. Furthermore, the caecal microbiota showed a significant change, with increased Defluviitaleaceae, Ruminococcaceae, and Coprococcus and reduced Lachnospiraceae and Allobaculum, which could mediate the detrimental effects of excess iron on gut health. We concluded that excessive iron exposure from liquid iron preparation induces oxidative stress and histopathological alterations in the intestine and liver. Impaired intestinal barrier function could increase iron transportation, and inflammation along with oxidative stress-enhanced liver iron deposition may cause further liver injury in a vicious circle. These effects were accompanied by lower intestinal segment damage and altered gut microbial composition of rats toward a profile with an increased risk of gut disease.
机译：本研究的目的是确定多余的铁在液体铁制剂（特别是肠道屏障功能）中的毒理学作用以及由过量铁引起的副作用或疾病的可能病因。在研究中，用1ml载体（0.01mol / L HCl）或1ml液体铁制剂，含有8mg，16mg或24mg铁的1ml 30天。评估铁状态，氧化应激，组织学（H＆E染色），超微结构（电子显微镜）和肠道和肝脏中的细胞凋亡（Turnel Assay）。通过16S rRNA测序评估盲肠微生物酵母。在研究2中，将20只具有与上述相同轮廓相同的大鼠，用1mL载体或24mg Fe进行口服饲养，30 d。肠道阻隔功能是通过体内研究和USSing室测定确定的;通过酶联免疫吸附试验观察到紧密结蛋白和血清促炎细胞因子。在研究1中，肠粘膜和肝脏表现出明显的氧化应激。此外，检测到向十二指肠肠细胞和肝细胞的铁浓度依赖性超微结构改变以及对结肠粘膜的组织学损伤。值得注意的是，在十二指肠肠细胞和肝细胞中增加了细胞凋亡。观察到肠道屏障障碍障碍障碍障碍和低表达，在结肠中比十二指肠更严重。血清血清炎性细胞因子更高表达的趋势可能表明系统性炎症。此外，疾病微生物群表现出显着的变化，随着Defluviitaleae，喇菇，喇叭杆菌和Coprococcus和降低的Lachnospiraceae和Allobaculum，这可能会介绍多余的铁对肠道健康的不利影响。我们得出结论，液体铁制剂的过度铁暴露在肠和肝脏中诱导氧化应激和组织病理学改变。肠道屏障功能受损可以增加铁运输，炎症以及氧化应激增强的肝脏铁沉积可能会导致恶性循环中的进一步肝损伤。这些效果伴随着肠道段损伤和改变大鼠的肠道微生物组成，朝向肠道疾病的风险增加。

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