Sulforaphane Restores Mitochondrial β-Oxidation and Reduces Renal Lipid Accumulation in a Model of Releasing Unilateral Ureteral Obstruction

Obstructive nephropathy (ON), characterized by urine flow disruption, can induce chronic kidney disease (CKD). Although the release of the obstruction is performed as the primary intervention, renal pathology often persists and progresses. Accordingly, the murine model of releasing unilateral ureteral obstruction (RUUO) is valuable for investigating the molecular events underlying renal damage after obstruction release. Remarkably, after RUUO, disturbances such as oxidative stress, inflammation, lipid accumulation, and fibrosis continue to increase. Mitochondrial dysfunction contributes to fibrosis in the UUO model, but its role in RUUO remains unclear. Additionally, the impact of using antioxidants to restore mitochondrial function and prevent renal fibrosis in RUUO has not been determined. This study aimed to determine the therapeutic effect of pre-administering the antioxidant sulforaphane (SFN) in the RUUO model. SFN was administered 1 day before RUUO to evaluate mitochondrial biogenesis, fatty acids (FA) metabolism, bioenergetics, dynamics, and mitophagy/autophagy mechanisms in the kidney. Our data demonstrated that SFN enhanced mitochondrial biogenesis and reestablished mitochondrial oxygen consumption and β-oxidation. These effects collectively reduced lipid accumulation and normalized mitochondrial dynamics, mitophagy, and autophagy, thereby mitigating fibrosis after obstruction. Our findings suggest that SFN holds promise as a potential therapeutic agent in ON-induced CKD progression in RUUO and opens new avenues in studying antioxidant molecules to treat this disease.