24 April 2019
Drugs defend against radiation exposure
Published online 22 October 2012
Accidents at nuclear power plants can result in people being exposed to harmful ionizing radiation (IR). In a person's defence, a cellular protein, nuclear factor-erythroid 2-related factor 2 (Nrf2), activates several antioxidant and anti-inflammation enzymes.
A study, jointly led by Jerry W. Shay and Tej K. Pandita from the University of Texas Southwestern Medical Center in Dallas and King Abdulaziz University in Jeddah, Saudi Arabia, has found that treating cells with two synthetic triterpenoids — a class of drugs originally designed to prevent and treat cancer — before IR exposure further activates Nrf2 triggering DNA repair.
The researchers first pretreated human colonic epithelial cells in the lab with the synthetic triterpenoid bardoxolonemethyl (BARD). Nrf2 degradation was inhibited, translocating Nrf2 into the cell nucleus, which then leads to activation of antioxidant response element (ARE) pathway and IR protection.
Mice colon tissues were used to evaluate the radioprotective effect of the second synthetic triterpenoid, CDDO-EA. Mice fed with CDDO-EA were protected from IR-induced cell damage and death in both the colon and small intestine. Pretreatment with CDDO-EA also increased mouse survival, which correlated with gastrointestinal tract protection and DNA damage signaling promotion following exposure to a lethal dose of IR.
These studies suggest that BARD and CDDO-EA are potent 'radioprotectors'. "We need better radioprotectors for first responders to nuclear accidents. CDDO-EA is non-toxic, orally available and could also be taken by cancer patients receiving radiation therapy," says Shay.
- Kim, S. B. et al. Targeting of Nrf2 induces DNA damage signaling and protects colonic epithelial cells from ionizing radiation. Proc. Natl. Acad. Sci. Unit. States. Am. (2012) doi:10.1073/pnas.1207718109