Silicon-based agent mitigates fatty liver formation in a CDAHFD60-induced MASH mouse model by enhancing hepatic function.

Abstract

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive hepatic condition driven by oxidative stress and fat accumulation, with rising global incidence linked to obesity and metabolic syndrome. A silicon (Si)-based agent that continuously produces molecular hydrogen upon contact with water was evaluated in a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD60)-induced MASH mouse model. The agent was incorporated at 2.5% into the diet and administered for 12 weeks. Despite the absence of macroscopic changes in liver appearance, histological analysis revealed reduced hepatic lipid droplet accumulation, attributed to amelioration of MASH-associated bile dysfunction. The Si-based agent also alleviated the hypolipidemia and body weight loss characteristic of this model, and attenuated systemic oxidative stress markers. Collectively, these findings indicate that continuous endogenous hydrogen generation via the Si-based agent improves both hepatic and systemic lipid metabolism while exerting antioxidant effects in MASH.

Mechanism

The Si-based agent reacts with water to continuously generate molecular hydrogen, which scavenges reactive oxygen species, thereby improving bile function, reducing hepatic lipid droplet accumulation, and attenuating systemic oxidative stress in MASH.