Rutin inhibits inflammatory responses by modulating purinergic enzymes and purine metabolism in Cryptococcus...

The aim of this study was to evaluate whether intraperitoneally administration of 50 mg rutin/kg body weight exerts a protective effect against Cryptococcus neoformans var. grubii-induced inflammatory damage by modulating serum purinergic enzymes and molecules. In a study, rats treated with a saline solution and infected with C. neoformans var. grubii demonstrated significant reductions (p < 0.05) in E-nucleoside triphosphate diphosphohydrolase (E-NTPDase) activity using adenosine triphosphate (ATP) as a substrate, as well as E-adenosine deaminase (E-ADA) activity, compared to the saline-treated uninfected group. Elevated extracellular ATP and adenosine (Ado) levels, along with increased serum interleukin-6 (IL-6) levels were observed (p < 0.05) in the C. neoformans var. grubii-infected group compared to the saline-treated uninfected group. No significant differences (p > 0.05) were noted in E-NTPDase activity for adenosine diphosphate (ADP), E-5'-nucleotidase activity, or levels of ADP and adenosine monophosphate between the groups. Treatment with rutin in infected animals effectively prevented these alterations (p > 0.05) when compared to the saline-infected group. In conclusion, purinergic signalling is involved in the pathogenesis of disseminated cryptococcosis, triggering different immunological responses depending on the specific enzyme involved, i.e., a pro-inflammatory response due to inhibition on E-NTPDase activity and an anti-inflammatory response due to inhibition on E-ADA activity. The intraperitoneal administration of 50 mg rutin/kg body weight exerted protective effects on purinergic signalling, preventing impairment on E-NTPDase and E-ADA activities and on ATP and Ado levels, thereby contributing to an improved immune response during disseminated cryptococcosis.