Reactive Dicarbonyl Scavenging with 2-Hydroxybenzylamine Improves MASH

Area of Science:

• Hepatology
• Biochemistry
• Oxidative Stress Research

Background:

• Lipid peroxidation produces reactive dicarbonyl electrophiles (DEs) implicated in disease.
• DEs contribute to oxidative stress, inflammation, and mitochondrial dysfunction in metabolic-associated steatotic liver disease (MASLD).
• Targeting DE stress presents a potential therapeutic avenue for MASLD management.

Purpose of the Study:

• To investigate the efficacy of the DE scavenger 2-hydroxybenzylamine (2-HOBA) in mitigating liver injury in MASLD.
• To determine if 2-HOBA reduces protein adduct formation by DEs in MASLD models.

Main Methods:

• Protein adducts were quantified in human livers via immunohistochemistry and immunoblotting.
• The therapeutic effects of 2-HOBA were evaluated in two distinct mouse models of MASLD: DIAMOND and STAM.
• Key biochemical and histological markers of liver injury and fibrosis were assessed.

Main Results:

• Human MASH livers showed increased isolevuglandin (IsoLG) protein adducts.
• 2-HOBA treatment in DIAMOND mice significantly reduced fibrosis scores and liver transaminases (AST, ALT).
• In STAM mice, 2-HOBA improved NAFLD activity scores, hyperglycemia, inflammatory cytokines, and reduced serum F2-isoprostanes (IsoPs).

Conclusions:

• DE scavenging with 2-HOBA demonstrates potential as a therapeutic strategy for MASLD.
• 2-HOBA may offer a non-invasive treatment to slow liver fibrosis and improve outcomes in MASLD patients.
• Further research, including studies in female subjects, is warranted to fully establish 2-HOBA's therapeutic role.