Esculetin improves inflammation of the kidney via gene expression against doxorubicin-induced nephrotoxicity in rats: In vivo and in silico studies

Examining the preventive potential and underlying mechanisms of Esculetin (E) in mitigating kidney damage induced by doxorubicin (DOX) in rats, this study also assessed the nephrotoxic effects when DOX was administered in combination with E. The experimental protocol involved a two-week treatment period with cumulative DOX doses (5 mg/kg), daily administration of E (50 mg/kg and 100 mg/kg), and the combined treatment of DOX with E50 and E100. The study delved into the gene expression levels of key regulatory factors associated with inflammation and apoptosis. Molecular analyses revealed that E effectively ameliorated the dysregulations induced by DOX at gene levels in the kidneys. Notably, the concurrent administration of E was observed to counteract the alterations in gene expressions induced by DOX significantly. E treatment decreased serum creatinine, albumin, and urea nitrogen levels in DOX-induced kidney damage. Furthermore, the docking analysis revealed that pi–cation, pi–pi stacking, and hydrogen bond interactions were the predominant molecular interactions within the binding pockets of these genes. This suggests that the nephroprotection provided by E involves the remodeling of inflammation and apoptosis pathways affected by DOX.