Award
NIH Reporter #5R21AI193780-02
Using a Superoxide Dismutase Mimetic to Mitigate Age-Associated, Radiation-Induced Cardiopulmonary Damage: Investigating the Role of Nitro-Oxidative Signaling and Mitochondrial Metabolism
Recipient
University of Iowa
Award Amount
$155,500.00
Ceiling
$155,500.00
Awarded
August 13, 2026
Identifier
5R21AI193780-02
This NIH-funded project studies the use of a superoxide dismutase mimetic to reduce age-related radiation-induced cardiopulmonary damage by targeting nitro-oxidative signaling and mitochondrial metabolism.
Description
An aging population faces unique health challenges, including increased susceptibility to ionizing radiation (IR) toxicities due to oxidative and nitrative metabolic changes. Elderly individuals are particularly vulnerable to IR-induced cardiopulmonary toxicities due to age-related physiological changes that impair tissue repair and regeneration. Age-associated decline in metabolic efficiency generates increased reactive oxygen species (superoxide). IR exposure may induce bursts of superoxide and nitrative species (nitric oxide). Excess superoxide can combine with nitric oxide to form peroxynitrite, damaging proteins, lipids, and DNA, leading to inflammation and fibrosis. This project investigates the impact of nitro-oxidative metabolism on mitochondrial electron transport chain (ETC) complex efficiency and cardiopulmonary physiology using genetically modified mice and an upper body irradiation model. It aims to assess the efficacy of a superoxide dismutase mimetic, Rucosopasem, in reducing oxidative stress and mitigating IR-induced cardiopulmonary effects, potentially unveiling targets to prevent or reduce such toxicities.