Arachidonic acid found to promote the occurrence of radiation-induced intestinal injury

In response to analysis revealed lately in Redox Biologya staff led by Prof. Han Wei from Hefei Institutes of Bodily Science (HFIPS), Chinese language Academy of Sciences (CAS) discovered, for the primary time, that dietary arachidonic acid (AA) promotes the incidence of radiation-induced intestinal harm (RIII).

RIII is a typical gastrointestinal complication (incidence fee is about 80%) attributable to radiotherapy on pelvic, belly, and retroperitoneal tumors. It could result in the interruption of radiotherapy. At current, no unified and efficient strategies can be found for scientific remedy of RIII. Subsequently, figuring out the pathogenesis of RIII is a crucial prerequisite for growing the methods for RIII remedy.

On this examine, the staff utilized RNA sequencing evaluation to research the doable involvement of ferroptosis in RIII mice’s intestinal tissue. In consequence, the degrees of lipid peroxidation markers, 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA), have been considerably elevated in these mice.

The researchers additionally found that Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, was profitable in mitigating each loss of life and intestinal fibrosis in RIII mice. Moreover, in cultured intestinal epithelial cells (IECs), organoids and mouse fashions, researchers discovered that AA, the omega-6 important fatty acidis a key consider radiation-induced ferroptosis. Exogenous AA triggered radiation-induced ferroptosis.

Subsequent mechanistic research revealed that the activation of STAT1-IRF1 positively regulated the expression of ACSL4, which promoted the incidence of ferroptosis after radiation. Alternatively, the AMPK signaling pathway was activated by AA and performed a detrimental regulatory function in radiation-induced ferroptosis.

The above outcomes indicated that the STAT1-IRF1-ACSL4 and AMPK signaling pathways have been potential molecular targets for the methods improvement of RIII prevention and remedy. Arachidonic acid, an important dietary fatty acid, was an necessary danger issue for ferroptosis-mediated RIII. This examine additionally advised that focused dietary diet management, which was anticipated to alleviate RIII, must be carried out throughout radiotherapy.