Effects of Psychological Stress and Alprazolam on Development of Oral Candidiasis in Rats

Psychological stress has been found to suppress cell-mediated immune responses that are important in limiting the proliferation of Candida albicans. Since anxiolytic drugs can restore cellular immunity in rodents exposed to stress conditions, we designed experiments conducted to evaluate the effects of alprazolam (1 mg/kg of body weight/day), a central benzodiazepine anxiolytic agonist, on the development of oral candidiasis in Sprague-Dawley rats exposed to a chronic auditory stressor. Animals were submitted to surgical hyposalivation in order to facilitate the establishment and persistence of C. albicans infection. Application of stress and treatment with drugs (placebo or alprazolam) were initiated 7 days before C. albicans inoculation and lasted until the end of the experiments (day 15 postinoculation). Establishment of C. albicans infection was evaluated by swabbing the inoculated oral cavity with a sterile cotton applicator on days 2 and 15 after inoculation, followed by plating on YEPD (yeast extract-peptone-dextrose) agar. Tissue injury was determined by the quantification of the number and type (normal or abnormal) of papillae on the dorsal tongue per microscopic field. A semiquantitative scale was devised to assess the degree of colonization of the epithelium by fungal hyphae. Our results show that stress exacerbates C. albicans infection of the tongues of rats. Significant increases in Candida counts, the percentage of the tongue's surface covered with clinical lesions, the percentage of abnormal papillae, and the colonization of the epithelium by fungal hyphae were found in stressed rats compared to those found in the unstressed rats. Treatment with alprazolam significantly reversed these adverse effects of stress, showing that, besides the psychopharmacological properties of this anxiolytic drug against stress, it has consequences for Candida infection.

已有研究表明，心理应激会抑制细胞介导的免疫应答，而这类应答对于限制白色念珠菌（Candida albicans）的增殖至关重要。鉴于抗焦虑药物可恢复应激状态下啮齿类动物的细胞免疫功能，本研究设计实验以评估阿普唑仑（alprazolam，1 mg/kg体重/日）——一种中枢苯二氮䓬类抗焦虑激动剂——对暴露于慢性听觉应激源的斯普拉格-道利（Sprague-Dawley）大鼠口腔念珠菌病发生发展的影响。为促进白色念珠菌感染的建立与持续，对受试动物实施了外科性唾液分泌减少术。于白色念珠菌接种前7天启动应激施加与药物干预（安慰剂或阿普唑仑），并持续至实验结束（接种后第15天）。通过在接种后第2天和第15天使用无菌棉拭子擦拭接种部位的口腔，随后将拭子接种于YEPD（酵母提取物-蛋白胨-葡萄糖）琼脂平板上，以此评估白色念珠菌感染的建立情况。通过对每个显微镜视野下舌背乳头的数量与类型（正常或异常）进行计数，来评估组织损伤程度。本研究设计了半定量评分量表，以评估上皮组织被真菌菌丝定植的程度。本研究结果显示，应激会加重大鼠舌部的白色念珠菌感染。与未应激大鼠相比，应激大鼠的念珠菌载量、临床病变覆盖的舌表面百分比、异常乳头百分比以及上皮被真菌菌丝定植的程度均显著升高。阿普唑仑干预可显著逆转应激带来的这些不良影响，这表明该抗焦虑药物除了具有对抗应激的精神药理学特性外，还可对白念珠菌感染产生干预作用。