N-Acetylcysteine Protection Against Radiation Induced Cellular Damage

Overview

Catheter ablation procedures (CAPs) are first line treatment for a great variety of cardiac arrhythmias. CAPs require X-Ray imaging; consequently, CAPs cause ionizing radiation (IR) exposure for patients. Exposure to IR, even at low-doses, increases individual risk of developing cancer. IR cause DNA damage directly and, mostly, indirectly by formation of cellular free radicals. Furthermore different response to IR results from inherited variants in genes involved in DNA damage repair. N-acetylcysteine (NAC) is an aminoacid that can directly neutralize free radicals and increase antioxidant systems. Our preliminary data suggest that IR exposure in patients undergoing CAP deranges the oxidative stress status and the pre-procedure intravenous administration of NAC could decrease such abnormality.

CARAPACE is a prospective, randomized, single-blinded, parallel-arm monocenter study. Eligible patients undergoing CAP at the Arrhythmology Unit of Centro Cardiologico Monzino will be enrolled. The hypothesis driving our study, based on published literature and our preliminary data, is that administration of antioxidant agents, before cardiac procedures involving IR exposure, might prevent IR harmful effects on human tissues in terms of reduction of systemic oxidative stress status and, in parallel, of oxidative DNA damage. The antioxidant agent tested in our study is NAC. NAC is a well-tolerated and safe medication and it has antioxidant properties is based on three main mechanisms: 1) direct antioxidant effect, 2) glutathione (GSH) precursor action, and 3) its activity in breaking thiolated proteins. Another hypothesis to be tested is whether genes involved in DNA damage repair could explain the great variability in patient radiosensitivity to IR exposure and whether these genes could affect NAC protective/healing effects.