p-Coumaric acid ameliorates ionizing radiation-induced intestinal injury through modulation of oxidative stress and pyroptosis

Intestinal injury is a clinical problem related to radiotherapy or accidental exposure to ionizing radiation. This study aimed to investigate the protective effect of p-coumaric acid (CA) against radiation induced intestinal injury. The present study orally administered CA to C57BL/6 male mice at 30 min before total body irradiation and continued for 3 days post irradiation. Then, the mice were sacrificed at day 3.5 or 14 after irradiation, respectively. The blood was collected to analyze the inflammatory cytokines. The antioxidant indexes of jejunum tissues were determined. Hematoxylin and eosin staining and apoptosis analysis was studied to investigate the pathological changes of the jejunum tissues. In addition, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were carried out to determine the changes in mRNA and protein levels of jejunum tissues. Compared with the only irradiated group, treatment with CA improved intestinal morphology and apoptosis, increased the villus height and the ratio of villus height to crypt depth. It also reduced the oxidative stress and inflammatory response. The molecular mechanism analysis showed that CA significantly inhibited the pyroptosis genes (Caspase-1, NLRP3 and AIM2) mRNA expression and improved the intestinal barrier genes expression. The results suggested that CA ameliorates ionizing radiation-induced intestinal injury by inhibition of oxidative stress, inflammatory response and pyroptosis.