15-Lipoxygenase-dependent radiomitigation by NO^●-Donors suppresses ferroptosis in intestinal Epithelium: Multiomics MS imaging and LC-MS evidence.

ABSTRACT: Threats of irradiation (IR) exposure increase the need for radiomitigators. An important contributor to radiation injury is ferroptosis, triggered by the disbalanced redox metabolism. We showed that 15-lipoxygenase (15-LOX) catalyzed peroxidation of arachidonoyl-phosphatidyl-ethanolamine is an essential ferroptotic response of ileum to total body IR (TBI). Given that nitric oxide (NO^● ) can suppress ferroptosis by inhibiting 15-LOX and by directly scavenging lipid radicals, we tested NO^●-donors with optimized half decay times as radiomitigators. Here, we report that diethylenetriamine-NONOate (DETA-NONOate) (with a half decay-time of 20 hr) acted as an effective radiomitigator when administered 24 hr after exposure to TBI (9.25Gy) and markedly prolonged survival of C5

SUBMITTER: Tyurina YY 

PROVIDER: S-EPMC12309946 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature