Comparative analysis of two immunosuppression protocols for vulvovaginal candidiasis induction in Wistar rats

Vulvovaginal candidiasis (VVC) is a prevalent public health problem worldwide. The frequent recurrences and treatment failures associated with existing therapies highlight the urgent need to explore new potential treatments. However, protocols for inducing vulvovaginal candidiasis in rodents are limited and lack standardization. Most approaches rely on immunosuppression to mimic human conditions. This study aimed to compare two immunosuppression protocols in a vulvovaginal candidiasis infection model using female Wistar rats. The animals were subjected to two immunosuppression: Chemical immunosuppression using cyclophosphamide (IMS) and a chronic unpredictable mild stress model (CUMS). Following the immunosuppression period, the rats were inoculated with C. albicans ATCC10231. After confirming the infection, the animals were treated with a vaginal cream containing clotrimazole (10 mg/g) or a vehicle for 7 days. During this period, behavioral parameters, food consumption, body weight, and vaginal microbial load were evaluated. At the end of treatment, the animals were euthanized, and blood, histological tissue, and microbiological parameters were analyzed. Animals subjected to the CUMS protocol exhibited significant behavioral changes, reduced food consumption, and impaired weight gain. They also displayed hematological and histological alterations, indicating severe immunosuppression and infection. Clotrimazole treatment failed to cure all animals in this group. In contrast, animals in the IMS protocol experienced milder immunosuppression, and clotrimazole treatment successfully cured all treated animals. The IMS method is more suitable for investigating primary vulvovaginal candidiasis infection compared to the CUMS method. The CUMS protocol induced more pronounced changes, such as weight loss and behavioral alterations, which may not accurately reflect primary VVC in humans. The IMS method, however, resulted in a vaginal infection with minimal systemic changes, more closely resembling the condition observed in women with primary VVC.