Butyric acid inhibits oxidative stress and inflammation injury in calcium oxalate nephrolithiasis by targeting CYP2C9.

Abstract

This study investigates the mechanism by which butyric acid can protect against calcium oxalate (CaOx) nephrolithiasis. To do so, a rat model was used with 0.75% ethylene glycol administration to induce CaOx crystal formation. Histological and von Kossa staining revealed calcium deposits and renal injury, while dihydroethidium fluorescence staining was used to detect reactive oxygen species (ROS) levels. Flow cytometry and TUNEL assays were used to assess apoptosis, respectively. Treatment with sodium butyrate (NaB) was found to partially reverse the oxidative stress, inflammation, and apoptosis associated with CaOx crystallization in the kidney. In addition, in HK-2cells, NaB reversed the decreased cell viability, increased ROS levels and apoptosis damage caused by oxalate exposure. Network pharmacology was employed to predict the target genes of butyric acid, CYP2C9. Subsequently, NaB was found to significantly reduce CYP2C9 levels in vivo and in vitro, and inhibition of CYP2C9 by Sulfaphenazole (a specific CYP2C9 inhibitor), was able to reduce ROS levels, inflammation injury, and apoptosis in oxalate-induced HK-2cells. Collectively, these findings suggest that butyric acid may inhibit oxidative stress and reduce inflammation injury in CaOx nephrolithiasis by suppressing CYP2C9.