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Effects of the Antifungal Agent Itraconazole on Proliferative Changes of the Forestomach Mucosa in Alloxan-induced Diabetic Rats

¹ Department of Pathology, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan;
² Laboratory of Molecular and Cellular Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University, Japan

Correspondence: Isao Narama, Department of Pathology, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan; e-mail:narama{at}pharm.setsunan.ac.jp.

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.

Key Words: antifungal agent • C. albicans • COX-2 • itraconazole • squamous cell carcinoma

Abbreviations: AL, alloxan • COX-2, cyclooxygenase-2 • ITCZ, itraconazole • SCC, squamous cell carcinoma • TBST, 50 mM Tris-HCl buffer (pH 7.6) with 0.03% Tween-20

This version was published on October 1, 2009

Toxicologic Pathology, Vol. 37, No. 6, 790-798 (2009)
DOI: 10.1177/0192623309344204


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