J Nutr Health.  2024 Dec;57(6):580-589. 10.4163/jnh.2024.57.6.580.

Hepatoprotective effects of an iron chelator, deferoxamine, in a mouse model of metabolic dysfunctionassociated fatty liver disease

• Choi JY
• Chung J

• KMID: 2564166
• DOI: http://doi.org/10.4163/jnh.2024.57.6.580

Abstract

Purpose
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent liver disorder linked to metabolic risk factors such as obesity. Iron overload has been shown to exacerbate MAFLD. This study examined the effects of deferoxamine (DFO), an iron chelator, on the progression of MAFLD in mice.
Methods
MAFLD was induced in male C57BL/6J mice by feeding them a high-fat diet along with high fructose and glucose in their drinking water. The mice were then divided into three groups and administered DFO (100 mg/kg body weight), liproxstatin-1 (Lip-1, 10 mg/kg), a ferroptosis inhibitor, or phosphate buffered saline as a vehicle control intraperitoneally for three weeks.
Results
DFO significantly reduced hepatic steatosis, inflammation, and ballooning degeneration, leading to a decrease in the MAFLD activity score (MAS). The serum aspartate aminotransferase and alanine aminotransferase levels were also significantly lower in the DFO group than in the vehicle group. DFO decreased the hepatic malondialdehyde levels, a marker of lipid peroxidation. In addition, DFO reduced the mRNA levels of fibrotic markers (collagen 1α1, collagen 3α1, and transforming growth factor β) and inflammatory cytokines (interleukin [IL]-6, IL-1β, and tumor necrosis factor α). DFO reduced the hepatic non-heme iron content and ferritin protein levels, while the apoptosis-inducing factor (AIF) protein levels were lowered without changes in glutathione peroxidase 4 (GPX4). Lip-1 exhibited comparable reductions in MAS, inflammatory and fibrotic markers, and hepatic AIF levels, while showing an increase in the hepatic GPX4 level.
Conclusion
The iron chelator DFO protects against steatosis, inflammation, and fibrosis in a mouse model of MAFLD, providing evidence for its potential use as a therapeutic agent for MAFLD.

Keyword

deferoxamine; fatty liver; iron; ferroptosis