title: Effects of the antifungal agent itraconazole on proliferative changes of the forestomach mucosa in alloxan-induced diabetic rats.
abstract: Alloxan-induced diabetic rats frequently exhibit proliferative lesions of squamous hyperplasia accompanied by chronic inflammation and Candida albicans infection in the forestomach, and some lesions progress to squamous cell carcinoma (SCC). Candida infection causes not only hyperplastic changes with inflammation but might also lead to SCC in human oral mucosa. Thus, the present study was conducted to examine the effects of the antifungal agent itraconazole (ITCZ) on proliferative and inflammatory changes of the forestomach in alloxan-induced diabetic WBN/Kob rats. Diabetes was induced by alloxan at fifteen weeks of age. Rats were allocated to three groups at forty-five weeks of age and were given ITCZ by gavage 0 (vehicle control), 5, and 10 mg/kg/day for four weeks, and they were sacrificed at the sixty-fifth week of age. Mucosal hyperplastic changes were consistently accompanied by inflammation and Candida infections in the 0 mg/kg group. These lesions were reduced by ITCZ (0 mg/kg; 100%, 5 mg/kg; 53.5%, 10 mg/kg; 61.5%). Squamous cell carcinoma was detected in three rats from the 0 mg/kg, but only one rat from the 10 mg/kg dose groups in this study. Itraconazole reduced the degree of mucosal hyperplasia, inflammatory changes, and Candida infection. Therefore, C. albicans infection was an important factor in pathogenesis of mucosal proliferation and inflammation.
authors.affiliation: Department of Pathology, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Sano
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Ozaki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kodama
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matsuura
authors.forename: Isao
authors.initials: I
authors.lastname: Narama
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans; D002177:Candidiasis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D006029:Glycosuria / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D006651:Histocytochemistry; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D006965:Hyperplasia; D017964:Itraconazole / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats
chemical_list: D000935:Antifungal Agents; D018809:Proliferating Cell Nuclear Antigen; D017964:Itraconazole; D051546:Cyclooxygenase 2