Selenomethionine alleviates LPS-induced septic kidney injury by regulating mitochondrial dynamics changes

Area of Science:

• Nephrology
• Immunology
• Biochemistry

Background:

• Sepsis-associated acute kidney injury (SA-AKI) is a significant clinical challenge.
• Inflammation and oxidative stress are key contributors to SA-AKI pathogenesis.
• The therapeutic potential of selenium, specifically selenomethionine (SeMet), in SA-AKI is largely unexplored.

Purpose of the Study:

• To investigate the protective effects and underlying mechanisms of SeMet against LPS-induced SA-AKI in a murine model.
• To evaluate SeMet's impact on renal inflammation, oxidative stress, and pathological damage.
• To elucidate SeMet's influence on mitochondrial dynamics, NF-κB signaling, and macrophage polarization.

Main Methods:

• A lipopolysaccharide (LPS)-induced murine model of SA-AKI was established in male C57BL/6 mice.
• Mice received weekly oral administration of SeMet (0.375 mg/kg) starting one week before LPS challenge.
• Renal function, inflammation markers, oxidative stress levels, pathological changes, mitochondrial dynamics, NF-κB pathway activation, and macrophage polarization were assessed.

Main Results:

• SeMet treatment significantly attenuated the inflammatory response and reduced oxidative stress in the kidneys.
• SeMet administration ameliorated renal pathological damage compared to control groups.
• Mechanistically, SeMet modulated mitochondrial dynamics, suppressed the NF-κB signaling pathway, and promoted M2 macrophage polarization.

Conclusions:

• Selenomethionine demonstrates significant protective effects against sepsis-induced acute kidney injury.
• SeMet mitigates SA-AKI by reducing inflammation, oxidative stress, and improving renal pathology.
• SeMet holds promise as a potential therapeutic agent for the prevention and treatment of SA-AKI.