Kupffer cell function in thyroid hormone-induced liver oxidative stress in the rat

Area of Science:

• Hepatology
• Endocrinology
• Immunology

Background:

• Thyroid hormones, particularly L-3, 3', 5-triiodothyronine (T3), play a crucial role in regulating cellular metabolism and function.
• Kupffer cells, the resident macrophages of the liver, are involved in various physiological and pathological processes, including immune response and detoxification.
• The interaction between thyroid hormone status and Kupffer cell activity in the context of liver function and oxidative stress remains an area of investigation.

Purpose of the Study:

• To investigate the influence of thyroid hormone (T3) on Kupffer cell function in the isolated perfused rat liver.
• To assess the impact of T3 on carbon uptake kinetics, cellular respiration, and markers of oxidative stress in the liver.
• To explore the potential protective effects of gadolinium chloride (GdCl3) against T3-induced changes in Kupffer cell function and liver viability.

Main Methods:

• Isolated perfused rat liver model was utilized to study Kupffer cell function.
• Colloidal carbon infusion was employed to measure carbon uptake rates and carbon-induced respiratory activity (O2 consumption).
• Assessment of thiobarbituric acid reactive substances (TBARS) formation, glutathione (GSH) levels, and lactate dehydrogenase (LDH) efflux were performed to evaluate oxidative stress and liver damage. Histological examination identified cell types involved in carbon uptake.

Main Results:

• Hyperthyroid (T3-treated) rat livers demonstrated significantly increased rates of carbon uptake and associated O2 consumption compared to euthyroid controls.
• T3 treatment led to increased hepatic O2 consumption, TBARS formation, GSH depletion, and enhanced sinusoidal LDH efflux, indicating heightened oxidative stress and cellular damage.
• Pretreatment with gadolinium chloride abolished the T3-induced enhancements in carbon uptake and respiratory activity, and significantly reduced T3-mediated changes in GSH and TBARS, preserving liver viability.

Conclusions:

• Hyperthyroidism significantly enhances Kupffer cell function in the rat liver, evidenced by increased carbon uptake and metabolic activity.
• The enhanced Kupffer cell function in hyperthyroidism contributes to increased oxidative stress within the liver, potentially through the generation of reactive oxygen species.
• Gadolinium chloride exhibits a protective effect, attenuating the hyperthyroidism-induced alterations in Kupffer cell function and mitigating oxidative stress in the liver.