Rutin attenuates oxidative damage-induced renal injury in rats experimentally infected with Cryptococcus neoformans by improving antioxidant capacity and reducing fungal burden.

Oxidative stress plays a pivotal role in the pathophysiology of infectious diseases, contributing to pathogenesis and the appearance of clinical symptoms. However, the involvement of oxidative stress in renal cryptococcosis remains unknown, as do the potential protective effects of rutin. Cryptococcus neoformans is considered the main agent of cryptococcosis, a systemic life-threatening opportunistic fungal disease that affects internal organs. In 2022, the World Health Organization classified it as a critical-priority group on its Fungal Priority Pathogens List. Rutin, a flavonoid with potent antioxidant and antifungal properties, has been proposed as a protective agent. Thus, this study aimed to evaluate whether 50 mg rutin/kg body weight prevents or reduces C. neoformans var. Grubii-induced renal oxidative stress. Renal fungal burden was significantly lower in rats that were treated with rutin and experimentally infected with C. neoformans, compared to those treated with saline solution and experimentally infected. Renal reactive oxygen species (ROS) and protein carbonylation levels were significantly higher in experimentally infected rats compared to uninfected controls, whereas catalase (CAT) and glutathione S-transferase (GST) activities were significantly lower. Treatment with rutin prevented the increase in renal ROS levels and the inhibition of CAT activity elicited by C. neoformans var. Grubii. However, no significant differences were observed in lipid damage or superoxide dismutase activity. This study is the first to demonstrate that C. neoformans var. Grubii infection induces renal oxidative damage in rats by promoting oxidative stress, increasing ROS levels, and impairing antioxidant defenses. Rutin treatment restored redox status in experimental rats through mechanisms involving oxidative stress. The protective effects of rutin against C. neoformans-induced kidney damage may result from its combined ability to scavenge ROS, inhibit protein damage, and enhance the antioxidant system.