Betanin mitigates vancomycin-induced acute kidney injury in mice and molecular docking indicated inhibition of STAT3 phosphorylation

Acute kidney injury (AKI) is a common, complicated disorder affecting hospitalized and critically ill patients. The signal transducer and activator of transcription-3 (STAT3) is associated with the progress of AKI. Betanin is a natural betacyanin with multiple biological activities. The contribution of STAT3 in vancomycin-induced AKI and possible protection by betanin were investigated in this study. Molecular docking and molecular dynamics simulation (MDS) studies were done to test the probability of inhibition of STAT3 phosphorylation by betanin. Further, the experiment included eighteen male albino mice were assigned as (i) saline group, (ii) AKI control group (received vancomycin 200 mg/kg) by intraperitoneal injection for 14 doses, and (iii) vancomycin + betanin (50 mg/kg) group. Serum urea and creatinine were measured. Frozen kidneys were used for measuring inflammatory markers, whereas formalin-fixed kidneys were cut into sections to prepare specimens stained with hematoxylin and eosin. Molecular docking showed that betanin can hinder STAT3 phosphorylation. Serum urea and creatinine were found elevated in the AKI group versus the saline group; but reduced in the vancomycin + betanin group. Further, histopathological examination indicated tubular degeneration and interstitial inflammation that was mitigated by betanin. Betanin attenuated vancomycin-induced AKI, enhanced kidney function parameters, and retained the integrity of renal histological structures. These effects were, at least partly, facilitated via inhibiting the phosphorylation of the upregulated STAT3. These results open an avenue to fully test the effect and mechanism of betanin in various models of kidney injuries.