Zinc Deficiency Induces Hepatic Oxidative Stress, Inflammation, and Programmed Cell Death in Mice

Area of Science:

• Hepatology
• Nutritional Biochemistry
• Cellular Biology

Background:

• Zinc deficiency is linked to oxidative stress, inflammation, and cell death.
• Understanding zinc's role in liver injury is crucial for public health.

Purpose of the Study:

• To investigate the impact of zinc deficiency on hepatic oxidative stress, inflammation, and programmed cell death.
• To explore the protective effects of zinc supplementation against zinc deficiency-induced liver injury.

Main Methods:

• Establishment of mouse models with varying zinc levels (normal, deficient, high) and an in vitro AML-12 hepatocyte model.
• Assessment of oxidative stress markers (ROS, MDA), antioxidant enzyme activity (SOD, CAT, GSH), inflammatory factors (NF-κB pathway, TNF-α, IL-6, IL-1β, IL-18, IL-10), and cell death pathways (apoptosis, necroptosis, pyroptosis).
• Quantitative real-time PCR, Western blot, and flow cytometry were employed for molecular and cellular analysis.

Main Results:

• Zinc deficiency significantly elevated reactive oxygen species and malondialdehyde, while inhibiting antioxidant enzymes in the liver.
• Inflammatory markers and pro-apoptotic/necroptotic/pyroptotic gene expression were upregulated, alongside increased hepatocyte apoptosis and inflammatory infiltration.
• Zinc supplementation effectively mitigated oxidative damage, suppressed inflammatory pathways, and reduced cell death markers.

Conclusions:

• Zinc deficiency activates programmed cell death through a multimodal pattern, contributing to liver injury.
• Zinc supplementation demonstrates therapeutic potential by alleviating oxidative stress, inflammation, and cell death.
• This study provides a theoretical foundation for addressing liver damage caused by imbalanced zinc intake.