title: Effect of SGLT2 inhibitors in a murine model of urinary tract infection with Candida albicans.
abstract: OBJECTIVE
  Urinary tract infection (UTI) is a common clinical problem in diabetic patients; however, the relationship between UTI and glucosuria remains uncertain. To investigate the relationship, we examined the effect of glucosuria induced by sodium glucose cotransporter 2 (SGLT2) inhibitors on the progression of UTI in mice.
  
  
  METHODS
  From 1 day before transurethral inoculation with Candida albicans, female mice were treated orally once a day with an SGLT2 inhibitor in different treatment regimens: (i) dapagliflozin at 10 mg/kg for 2, 3 or 7 days, (ii) dapagliflozin at 0.1, 1 or 10 mg/kg for 3 days and (iii) dapagliflozin, canagliflozin or tofogliflozin at 10 mg/kg for 3 days. To evaluate the ascending UTI, the kidneys were removed 6 days after the inoculation, and the number of viable C. albicans cells in kidney was measured as colony-forming units (CFU).
  
  
  RESULTS
  In mice treated with dapagliflozin, the number of C. albicans CFU in kidney increased in accordance with both treatment duration and dose. The number of CFU significantly increased when mice were treated with 10 mg/kg dapagliflozin or canagliflozin but not tofogliflozin. With dapagliflozin and canagliflozin, urine glucose concentration (UGC) significantly increased up to 24 h after drug administration; with tofogliflozin, UGC significantly increased only up to 12 h after drug administration.
  
  
  CONCLUSIONS
  Our data indicate that increased susceptibility to UTI is associated with a persistent increase in UGC.
authors.affiliation: Research Division, Chugai Pharmaceutical Co. Ltd., Gotemba, Shizuoka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Hiramatsu
authors.forename: M
authors.initials: M
authors.lastname: Fukazawa
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: K
authors.initials: K
authors.lastname: Honda
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Y
authors.initials: Y
authors.lastname: Kawabe
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D000068896:Canagliflozin; D002176:Candida albicans / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy*; D018450:Disease Progression; D005260:Female; D005960:Glucosides / Q000494:pharmacology*; D006029:Glycosuria / Q000382:microbiology; D007668:Kidney / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes / Q000494:pharmacology*; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes; D000068896:Canagliflozin; C529054:dapagliflozin; C575086:6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol
keywords: SGLT2 inhibitor; antidiabetic drug; diabetic complications; experimental pharmacology; renal glucose handling; type 2 diabetes; urinary tract infection