Prophylactic and Therapeutic Role of Vitamin D3 in Combination with Fluconazole Against Vaginal Candidiasis in a Murine Model

Abstract

Objective: In the present study, we assessed the adjunct effect of vitamin D3 in combination with Fluconazole (FLZ) against Vulvovaginal Candidiasis (VVC) in mice. Methods: Prophylactic effect was assessed by pretreating mice with vitamin D3 before exposure of mice with 2 X 106 CFUs of Candida albicans followed by treatment with FLZ. To determine the combined therapeutic efficacy, C. albicans infected mice were treated with a combination of vitamin D3 (10 μg/kg) and FLZ (10 and 20 mg/kg). The efficacy of the treatment was assessed by analyzing the fungal load and blood cell count. Moreover, the levels of inflammatory cytokines, including IL- 1β, IL-17 and TNF-α, were analyzed in the vaginal tissues. The histological analysis of the vaginal tissue from the untreated and treated mice was performed to assess the efficacy of the treatment. Results: Prophylactic treatment with vitamin D3 (10 and 20 μg/kg) significantly increased the therapeutic effect of FLZ against VVC. In a therapeutic experiment, mice in the infected control group showed the highest vaginal fungal load of 83627 ± 10058 CFUs. Treatment with FLZ at a dose of 10 mg/kg reduced fungal load to 55523 ± 14823 CFUs, whereas the mice treated with a combination of vitamin D3 and FLZ (10 mg/kg) had the fungal burden of 12156 ± 3219. Similarly, treatment with FLZ (20 mg/kg) reduced fungal load to 36394 ± 5648 CFUs, whereas the addition of vitamin D3 to FLZ (20 mg/kg) further reduced the fungal burden to 2179 ± 1188. The leukocyte numbers in the infected mice increased to 9802 ± 505 as compared to 5152 ± 778 in normal control mice. Whereas, a combination of vitamin D3 with FLZ (10 and 20 mg/kg) reduced leukocyte numbers to 7284 ± 607 and 5739 ± 1126. The histological analysis data revealed epithelial necrosis, shedding and ulceration in the vaginal wall. Treatment with FLZ or a combination of FLZ and vitamin D3 brought regenerative changes in the vaginal epithelium and lamina proparia. Conclusion: The results of the present work recommend that the addition of vitamin D3 may be considered to increase the efficacy of FLZ against VVC.