Arachidonic acid enhances ferroptosis leading to occurrence of radiation-induced intestinal injury

China: A recent study for the first time has shown dietary arachidonic acid (AA) promotes the occurrence of radiation-induced intestinal injury (RIII).

The research, published in Redox Biology was led by Prof. HAN Wei from Hefei Institutes of Physical Science (HFIPS), Chinese Academy of Sciences (CAS). 

RIII is a common gastrointestinal complication (incidence rate is about 80%) caused by radiotherapy on pelvic, abdominal, and retroperitoneal tumours. It may lead to the interruption of radiotherapy. At present, no unified and effective methods are available for the clinical treatment of RIII. Therefore, determining the pathogenesis of RIII is an important prerequisite for developing the strategies for RIII treatment.

In this study, the team utilized RNA sequencing analysis to investigate the possible involvement of ferroptosis in RIII mice's intestinal tissue. As a result, the levels of lipid peroxidation markers, 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA), were significantly elevated in these mice.

The researchers also discovered that Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, was successful in mitigating both death and intestinal fibrosis in RIII mice. Furthermore, in cultured intestinal epithelial cells (IECs), organoids and mouse models, researchers found that AA, the omega-6 essential fatty acid, is a key factor in radiation-induced ferroptosis. Exogenous AA triggered radiation-induced ferroptosis.