Work

Mitochondrial Quality Control Systems in Septic AKI: Molecular Mechanisms and Therapeutic Implications

Year: 2025

Type: article

Abstract: Objectives: Despite significant advancements in medical treatments, the creation of a successful treatment strategy for acute kidney injury (AKI) remains a pressing concern.Given the well-documented clinical benefits of canagliflozin in renal protection, our research focused on exploring the possible therapeutic benefits of canagliflozin in treating AKI, with a focus on its underlying mechanisms of action.Methods: To induce AKI, we utilized lipopolysaccharide (LPS) in the presence of canagliflozin, allowing us to assess the drug's effects on kidney function and structure.Results: Our results indicate that canagliflozin lowered blood urea nitrogen and serum creatinine concentrations while enhancing tubular architecture in rodents with LPS-triggered septic AKI.It additionally diminished inflammation, oxidative damage, and tubular cell apoptosis.In vitro, canagliflozin maintained mitochondrial functionality in LPS-exposed HK-2 cells by stabilizing membrane potential, reducing ROS generation, and normalizing respiratory chain activity.Its benefits were facilitated through the AMPKα1/PGC1α/NRF1 axis, promoting mitochondrial regeneration.Importantly, blocking this pathway or employing AMPKα1-deficient animals negated canagliflozin's protective effects, highlighting the essential role of AMPKα1 in its kidney-protective mechanisms.Conclusion: Our investigation implies that canagliflozin might represent a viable treatment strategy for septic AKI, operating through the stimulation of the AMPKα1/PGC1α/NRF1 axis to preserve kidney performance and structural integrity.These findings warrant further investigation into the clinical potential of canagliflozin in this context.

Source: International Journal of Medical Sciences

DOI: 10.7150/ijms.107012