Oral administration of silicon-based agents attenuates renal fibrosis

Abstract

Renal fibrosis occurs during renal failure progression and is exacerbated by oxidative stress. Oral silicon-based agents generate high intestinal hydrogen levels and reduce systemic oxidative stress. Therefore, in this study, we aimed to verify the efficacy of silicon-based agents against renal fibrosis and elucidate their underlying mechanisms in a unilateral ureteral obstruction mouse model. The mice were grouped based on the treatment provided. Comparisons between the groups were performed on postoperative days 1 and 14. On postoperative day 14, renal fibrosis, tubular cell apoptosis, and transforming growth factor-β and 4-hydroxy-2-nonenal expression were significantly reduced in the silicon-treated group (P < 0.05). Following RNA-sequencing on tissues extracted on postoperative day 14, pathway enrichment analysis was performed, revealing significant downregulation of various pathways associated with tissue fibrosis in mice in the silicon-treated group. Using tissues extracted on postoperative day 1, RNA sequencing and immunohistochemical analysis were performed. We found that complement component 3 expression was significantly reduced in mice treated with a silicon-based agent. Oxidative stress, tubular cell death, pro-fibrotic factors, and renal fibrosis were suppressed in our model following treatment with a silicon-based agent. Moreover, complement component 3 activity was inhibited during the early postoperative phase. Here, we showed that silicon-based agents represent potential novel therapeutic options against renal fibrosis.

Keywords: Fibrosis; Hydrogen; Kidney; Oxidative stress; Si-based agent.