Iron overload activates NF-κB-driven hepatic inflammation in suckling rats

Area of Science:

• Pediatric Nutrition
• Hepatology
• Immunology

Background:

• Iron is vital for infant development, but excessive intake poses risks to the vulnerable neonatal liver.
• The precise mechanisms linking high iron intake to liver damage in infants are not fully understood.
• The neonatal period is critical for liver and immune system development, making the liver susceptible to iron overload.

Purpose of the Study:

• To investigate the impact of high iron supplementation on liver structure and function in infant rats.
• To elucidate the molecular mechanisms underlying iron overload-induced liver injury during the suckling period.

Main Methods:

• Suckling rats received varying iron supplementation levels (10, 50, 100 mg Fe/kg).
• Hepatic structure, intermediary metabolism, and immune responses were analyzed.
• Key signaling pathways (NF-κB, Nrf2/HO-1) and inflammatory markers were assessed.

Main Results:

• High iron doses (50 and 100 mg/kg) led to liver inflammation, elevated ALT and AST levels.
• Iron overload promoted M1 macrophage polarization, increasing pro-inflammatory cytokines (IL-6, TNF-α, IL-1β) and activating the NF-κB pathway.
• Excessive iron induced oxidative stress, activating the Nrf2/HO-1 antioxidant pathway, but this response was insufficient to mitigate inflammation.

Conclusions:

• Excessive iron intake during suckling activates the NF-κB pathway, promoting M1 macrophage polarization and inflammation, ultimately impairing liver health.
• This study reveals mechanisms of iron overload-induced liver damage in infants, offering a basis for treating related conditions.
• Findings highlight the critical need to manage iron supplementation in infants to prevent liver damage.