Potential use of HMG-CoA reductase inhibitors (statins) as radioprotective agents.
HMG-CoA reductase inhibitors (statins) are widely used in the therapy of hypercholesterolemia. Apart from their lipid-lowering activity, they have pleiotropic effects that are attributed to the inhibition of regulatory proteins, including Ras-homologous (Rho) GTPases. Here, we discuss the potential usefulness of statins to prevent normal tissue damage provoked by radiotherapy. Statins reduce the mRNA expression of pro-inflammatory and pro-fibrotic cytokines stimulated by ionizing radiation in vitro and alleviate IR-induced inflammation and fibrosis in vivo. The currently available data indicate that statins accelerate the rapid repair of DNA double-strand breaks and, moreover, mitigate the DNA damage response induced by IR. Furthermore, statins increase the mRNA expression of DNA repair factors in vivo. Thus, although the molecular mechanisms involved are still ambiguous, preclinical data concordantly show a promising radioprotective capacity of statins.
University Medical Center of the Johannes Gutenberg University Mainz, Institute of Toxicology, Germany. fritz@uni-mainz.de
Gerhard
G
Fritz
Christian
C
Henninger
Johannes
J
Huelsenbeck
D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D011832:Radiation Injuries / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D011878:Radiotherapy / Q000009:adverse effects
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011837:Radiation-Protective Agents