Exploring the Potential Targets and Molecular Mechanisms of Selenomethionine to Attenuate Acute Kidney Injury Based...

Renal ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury. Selenomethionine, as a highly effective antioxidant and anti-inflammatory agent, shows promising application prospects in disease treatment. However, research on the role and mechanisms of selenomethionine in renal IRI remains relatively scarce. This study comprehensively analyzed the potential targets and mechanisms of action by which selenomethionine alleviates renal IRI through the integration of network pharmacology, molecular simulation techniques, and animal experiments. Concurrently, we employed the mitogen-activated protein kinase (MAPK) signaling pathway agonist anisomycin for intervention to validate the mechanism of action of selenomethionine. Through network pharmacology, we identified glutathione peroxidase 3 (GPX3) and interleukin-6 (IL6) as target molecules for selenomethionine. The predictive models constructed for these two molecules demonstrate good diagnostic value for renal IRI. Molecular simulation techniques' results demonstrate that selenomethionine exhibits strong binding affinity with GPX3 and IL6, forming highly stable complexes. Animal studies have demonstrated that selenomethionine can increase GPX3 expression levels and inhibit IL-6 secretion. Simultaneously, intervention with selenomethionine significantly suppressed inflammatory responses and alleviated renal IRI. Using ssGSEA and animal experiments, we demonstrated that selenomethionine may exert its protective effects by inhibiting the MAPK signaling pathway. Finally, following anisomycin intervention, it was observed that when selenomethionine's inhibitory effect on the MAPK signaling pathway was reversed, GPX3 expression decreased and IL-6 secretion increased again, thereby reversing selenomethionine's protective effect. This study demonstrates that GPX3 and IL-6 may serve as potential targets for selenomethionine in alleviating renal IRI. Furthermore, selenomethionine may mitigate renal IRI by suppressing the MAPK signaling pathway.