Publication: Increased susceptibility to dextran sulfate-induced mucositis of iron-overload β-thalassemia mice, another endogenous cause of septicemia in thalassemia
Issued Date
2021-06-01
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ISSN
14708736
01435221
01435221
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2-s2.0-85108248392
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Mahidol University
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SCOPUS
Bibliographic Citation
Clinical Science. Vol.135, No.12 (2021), 1467-1486
Suggested Citation
Peerapat Visitchanakun, Wimonrat Panpetch, Wilasinee Saisorn, Piraya Chatthanathon, Dhammika Leshan Wannigama, Arthid Thim-Uam, Saovaros Svasti, Suthat Fucharoen, Naraporn Somboonna, Asada Leelahavanichkul Increased susceptibility to dextran sulfate-induced mucositis of iron-overload β-thalassemia mice, another endogenous cause of septicemia in thalassemia. Clinical Science. Vol.135, No.12 (2021), 1467-1486. doi:10.1042/CS20210328 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/78140
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Title
Increased susceptibility to dextran sulfate-induced mucositis of iron-overload β-thalassemia mice, another endogenous cause of septicemia in thalassemia
Abstract
Enterocyte damage and gut dysbiosis are caused by iron-overload in thalassemia (Thl), possiblymaking the gut vulnerable to additional injury. Hence, iron-overload in the heterozygous β-globin deficient (Hbbth3/+) mice were tested with 3% dextran sulfate solution (DSS). With 4 months of iron-gavage, iron accumulation, gut-leakage (fluorescein isothiocyanate dextran (FITC-dextran), endotoxemia, and tight junction injury) in Thl mice were more prominent than WT mice. Additionally, DSS-induced mucositis in iron-overloaded mice from Thl group was also more severe than theWT group as indicated by mortality, liver enzyme, colon injury (histology and tissue cytokines), serum cytokines, and gut-leakage (FITC-dextran, endotoxemia, bacteremia, and the detection of Green-Fluorescent Producing Escherichia coli in the internal organs after an oral administration). However, Lactobacillus rhamnosus GG attenuated the disease severity of DSS in iron-overloaded Thl mice as indicated by mortality, cytokines (colon tissue and serum), gut-leakage (FITC-dextran, endotoxemia, and bacteremia) and fecal dysbiosis (microbiome analysis). Likewise, Lactobacillus conditioned media (LCM) decreased inflammation (supernatant IL-8 and cell expression of TLR-4, nuclear factor κB (NFκB), and cyclooxygenase-2 (COX-2)) and increased transepithelial electrical resistance (TEER) in enterocytes (Caco-2 cells) stimulated by lipopolysaccharide (LPS) and LPS plus ferric ion. In conclusion, in the case of iron-overloaded Thl, therewas a pre-existing intestinal injury that wask more vulnerable to DSS-induced bacteremia (gut translocation). Hence, the prevention of gut-derived bacteremia and the monitoring on gut-leakage might be beneficial in patients with thalassemia.