Hyperglucosuria induced by dapagliflozin augments bacterial colonization in the murine urinary tract
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Le résumé fourni par la source
AIM: To test the effects of dapagliflozin-induced hyperglucosuria on ascending bacterial urinary tract infection (UTI) in a mouse model. METHODS: Dapagliflozin or canagliflozin was used to induce hyperglucosuria in non-diabetic adult female mice prior to transurethral inoculation with uropathogenic Escherichia coli (UPEC) or Klebsiella pneumoniae. Glucose, bacterial load, cytokines, neutrophil mobilization and inflammation during acute and chronic UTI were determined. RESULTS: Significant increase in UPEC load was observed in the urinary tract of hyperglucosuric mice compared with controls. Dapagliflozin-treated mice developed bacteraemia resulting in UPEC colonization of the spleen and liver at a higher frequency than controls. Chronic UTI in hyperglucosuric mice resulted in an increased incidence of renal abscesses. Histopathological evaluation revealed only modest increases in tissue damage in the urinary bladders and kidneys of dapagliflozin-treated mice, despite a profound increase in bacterial load. There was poor neutrophil mobilization to the urine of hyperglucosuric mice. We also observed a delayed increase of IL-1β in urine, and bladders, and IL-6 in urine of hyperglucosuric mice. Experimental inoculation with K. pneumoniae also revealed higher bacterial burden in the urinary bladder, spleen and liver from dapagliflozin-treated mice compared with controls. CONCLUSION: Collectively, our results indicate that dapagliflozin-induced hyperglucosuria in non-diabetic female mice leads to increased susceptibility to severe UTI, and bacteraemia of urinary tract origin.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Hyperglucosuria induced by dapagliflozin augments bacterial colonization in the murine urinary tract
- Date Crossref
- 18/05/2020
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Texas A&M University pays non établi dans la noticeUniversité ou école supérieure
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Wake Forest University pays non établi dans la noticeUniversité ou école supérieure
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College of Veterinary Medicine and Biomedical Sciences Texas A& Department of Veterinary Pathobiology pays non établi dans la noticeUniversité ou école supérieure
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Department of Microbiology and Immunology Wake Forest School of Medicine Winston‐Salem North Carolina USA Department of Microbiology and Immunology pays non établi dans la noticeUniversité ou école supérieure
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Department of Pathology Wake Forest School of Medicine Winston‐Salem North Carolina USA Section on Comparative Medicine pays non établi dans la noticeUniversité ou école supérieure
Texas A&M University, Wake Forest University et Department of Veterinary Pathobiology — College of Veterinary Medicine and Biomedical Sciences Texas A&, avec 2 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.