Guanosine protects against glycerol-induced acute kidney injury via up-regulation of the klotho gene

Acute Kidney Injury (AKI) is characterized by a rapid and reversible decline in renal function with a rapid decrease in Glomerular Filtration Rate (GFR), which is associated with high mortality. Rhabdomyolysis accounts for 10-40% of AKI, to which the therapeutic approach is limited. is a protein that modulates sodium-phosphate co-transporters, ion channels that have been reported to have a renal protective effect. Guanosine, a purine nucleoside, has already been reported to have a renal protective effect; however, the mechanism of such protection and its relation to modification has not been evaluated yet. This study aims to evaluate the mechanism of the protective effect of guanosine against rhabdomyolysis-induced AKI and its relation to the expression of the gene. In the current study, rats were divided into three groups: control, glycerol-induced AKI, and guanosine-treated. Serum urea and creatinine levels, renal tissue Total Antioxidant Capacity (TAC), and and genes expression were evaluated. Furthermore, caspase-3 immunostaining and histopathological evaluations were done. Results showed that guanosine treatment resulted in a significant reduction in serum urea and creatinine, genes expression, and caspase-3 immunoexpression, and an increase in TAC and genes expression. Results also revealed an improvement of renal histopathology when compared with the glycerol-induced AKI group. Guanosine may be a promising agent in the treatment of rhabdomyolysis-induced AKI. The proposed mechanism for guanosine may be through its ability to enhance gene expression in renal tissue, with subsequent antioxidant and anti-apoptotic activity.