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

Objective(s): 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 ۱۰–۴۰% of AKI, to which the therapeutic approach is limited. Klotho 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 Klotho 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 Klotho gene.Materials and Methods: 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 Klotho and Cystatin C genes expression were evaluated. Furthermore, caspase-۳ immunostaining and histopathological evaluations were done. Results: Results showed that guanosine treatment resulted in a significant reduction in serum urea and creatinine, Cystatin C genes expression, and caspase-۳ immunoexpression, and an increase in TAC and Klotho genes expression. Results also revealed an improvement of renal histopathology when compared with the glycerol-induced AKI group. Conclusion: 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 Klotho gene expression in renal tissue, with subsequent antioxidant and anti-apoptotic activity.

Keywords:

Acute kidney injury , Caspase-۳ , Glycerol , Guanosine , Klotho , rhabdomyolysis