Rutin prevents memory impairment by reducing brain oxidative stress and fungal burden in a rat model of cryptococcosis.

The aim of this study was to examine whether intraperitoneal (ip) rutin administration is able to reduce or prevent Cryptococcus neoformans var. grubii-induced brain damage, as well as lower fungal burden in male Wistar rats. Inhibitory avoidance tasks revealed memory impairments in rats experimentally infected with C. neoformans var. grubii when compared to saline or uninfected rats. Rutin administration to infected rats prevented memory loss. Brain reactive oxygen species, thiobarbituric acid reactive substances, and nitric oxide levels were significantly higher in rats infected with C. neoformans var. grubii compared to saline or uninfected animals. Rutin administration to infected rats decreased (61%, 33%, and 58%, respectively) all these alterations. Brain catalase (CAT) activity and total antioxidant capacity (TAC) levels were significantly diminished in rats infected with C. neoformans var. grubii compared to saline or uninfected rats, while rutin administration to infected rats blocked reductions in brain TAC levels and partially restored brain CAT activity. Finally, administration of rutin decreased (49%) brain fungal burden compared to saline or uninfected rats. Summary data demonstrated that oxidative stress was involved in C. neoformans var. grubii-induced memory impairment. The novelty of the study is that rutin ameliorated C. neoformans var. grubii-initiated memory loss via stimulation of the antioxidant defense system protecting the brain against free radical-mediated effects and lipid peroxidation, as well as exerting antifungal action. Thus, rutin may be considered as a potential source for cryptococcosis treatment.