National Cancer Center researchers have discovered a mechanism for liver regeneration in animal models triggered almost immediately after episodes of severe liver damage.

The study, reported in MedicalXpress, explains that the liver is necessary for proper digestion, eliminating toxins and it is crucial for regeneration to replace damaged liver cells.

The process occurs within several minutes following severe liver damage with glutamate, an amino acid, in control.

However, it does not regenerate when faced with diseases such as cirrhosis involving chronic liver damage.

The authors of the study believe that supplementing nutritional glutamate will be successful in promoting liver regeneration. It will provide benefits to patients who have chronic and severe damage to their liver.

The study’s senior author, Nabil Djouder, points out that an unhealthy lifestyle and diet affects liver regeneration. He is joined by first author Maria Rigual who explained that in previous years liver regeneration was recognized as occurring through primary functional cells (hepatocytes), but the concept was not fully understood.

The new discovery is considered to be novel in that it refers to the bone marrow and liver, two distinctly different organs, as well as the immune system.

Rapid Chain of Events

Results of the study show that after damage to the liver:

• Hepatocytes create glutamate which enters the bloodstream where it activates immune system cells called macrophages that secrete a growth factor leading to
• An increase in hepatocyte production

These events allow glutamate to activate its own liver regeneration rapidly, within minutes, by way of macrophage metabolism. The researchers agree that this is a complex but ingenious view of the way in which the liver creates regeneration.

Coordination during Regeneration

The study defines the way in which various regions in the liver react during regeneration. The liver contains different forms of hepatocytes that perform separate metabolic functions in various areas.

Hepatocytes produce glutamine synthetase, a protein that maintains glutamate levels and is a critical part of regeneration.

The researchers further explained that inhibiting glutamine synthetase brings additional glutamate into circulation and accelerates the regeneration of the liver.

When the liver receives acute damage, the cycle looks somewhat like this:

• Glutamine synthase suffers a decrease and blood glutamate activity increases
• Bone marrow connection is established
• Macrophages are reprogrammed
• Hepatocyte growth is stimulated

The scientists see dietary glutamate supplements as being recommended after surgical removal of tissue or a body part. Supplementation may also be used in the process of reducing damage from cirrhosis.

Glutamate supplements may be of benefit to individuals who have had liver resection to remove tumors.

Source: MedicalXpress

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