Radiation affects liver function primarily by causing direct damage to liver cells, known as hepatocytes, through mechanisms involving oxidative stress, inflammation, and cell death. When the liver is exposed to radiation, such as during cancer treatment or accidental exposure, the energy from radiation generates reactive oxygen species (ROS). These ROS are highly reactive molecules that can damage cellular components including DNA, proteins, and lipids, leading to oxidative stress. This oxidative stress disrupts normal cellular function and triggers inflammatory responses within the liver tissue.
The inflammation caused by radiation exposure involves the activation of various signaling pathways, including the NF-κB pathway, which plays a central role in regulating immune and inflammatory responses. Activation of this pathway leads to the production of inflammatory cytokines that further exacerbate liver injury. This inflammatory environment can cause hepatocytes to undergo apoptosis, a form of programmed cell death, reducing the number of functional liver cells and impairing the liver’s ability to perform its vital functions such as detoxification, protein synthesis, and metabolism.
Radiation-induced liver injury often progresses through a cascade of events starting with cellular damage and inflammation, followed by fibrosis, where excessive connective tissue builds up in the liver. This fibrosis can impair blood flow and disrupt the liver’s architecture, leading to chronic liver dysfunction. In severe cases, this can progress to radiation-induced liver disease (RILD), characterized by jaundice, ascites, and liver failure.
At the molecular level, radiation affects key regulatory pathways that control cell survival and metabolism. For example, the LKB1/AMPK/mTOR pathway, which is involved in energy sensing and autophagy (the process by which cells remove damaged components), is modulated during radiation exposure. Activation of autophagy can be protective by clearing damaged organelles and proteins, but excessive or dysregulated autophagy may contribute to liver cell death.
Certain natural compounds, such as curcumin, have been studied for their ability to mitigate radiation-induced liver damage. Curcumin can inhibit the NF-κB pathway, reducing oxidative stress, inflammation, and apoptosis, thereby protecting liver cells from radiation injury. Similarly, drugs that modulate the LKB1/AMPK/mTOR pathway show promise in attenuating hepatotoxicity caused by radiation.
The liver’s response to radiation is complex and depends on factors such as the dose and duration of radiation exposure, the liver’s baseline health, and the presence of other stressors or diseases. Because the liver is a highly vascular and metabolically active organ, damage to its cells can have widespread effects on the body’s overall metabolism and immune function.
In summary, radiation impairs liver function by inducing oxidative stress and inflammation that damage hepatocytes, triggering cell death and fibrosis. This disrupts the liver’s ability to carry out essential metabolic and detoxifying roles. Understanding these mechanisms has led to research into protective agents that can reduce liver injury during radiation exposure, aiming to preserve liver function and improve outcomes for patients undergoing radiation therapy.