Pravastatin reduces radiation-induced damage in normal tissues

Abstract

Pravastatin is an inhibitor of 3-hydroxy-3-methyl- glutaryl-coenzyme A reductase that has been reported to have therapeutic applications in a range of inflammatory conditions. The aim of the present study was to assess the radioprotective effects of pravastatin in an experimental animal model. Mice were divided into two groups: The control group received ionizing radiation with no prior medication, while the pravastatin group received pravastatin prior to ionizing radiation. Pravastatin was administered orally at 30 mg/kg body weight in drinking water at 24 and 4 h before irradiation. Intestinal crypt epithelial cell survival and the incidence of apoptosis in the intestine and lung were measured post-irradiation. The effect of pravastatin on intestinal DNA damage was determined by immunohistochemistry. Finally, the effect of pravastatin on tumor response to radiotherapy was examined in a mouse mesothelioma xenograft model. Pravastatin increased the number of viable intestinal crypts and this effect was statistically significant in the ileum (P<0.0001). The pravastatin group showed significantly lower apoptotic indices in all examined parts of the intestine (P<0.0001) and tended to show reduced apoptosis in the lung. Pravastatin reduced the intestinal expression of ataxia-telangiectasia mutated and gamma-H2AX after irradiation. No apparent pravastatin-related differences were observed in the response of xenograft tumors to irradiation. In conclusion, pravastatin had radioprotective effects on the intestine and lung and reduced radiation-induced DNA double-strand breaks. Pravastatin may increase the therapeutic index of radiotherapy.

Radiation-induced heart disease: a review of classification, mechanism and prevention

“…Zang et al further confirmed through experiments that atorvastatin can reduce radiation-induced myocardial fibrosis by inhibiting multiple inflammatory responses and OS pathway activation 104. Doi et al showed that pravastatin could also protect tissue damage caused by radiation by reducing DNA double-strand breakage in normal tissue cells 113. However, it has been reported that atorvastatin can improve the repair of oxidative DNA damage in vascular smooth muscle cells (VSMCs) without affecting the initial level of DNA damage114.…”

Nuclear and Radiological Emergencies: Biological Effects, Countermeasures and Biodosimetry

“…GT3 and simvastin provide synergic protection against radiation-induced lethality, hematopoietic and bone marrow injury compared to the single treatments [ 196 ]. Pravastatin [ 300 ] and atorvastatin [ 301 ] have also shown radiomitigative efficacy.…”

Myocardial Ischemia Related to Common Cancer Therapy—Prevention Insights

“…In animal and cell culture models, statins ameliorated radiation-induced inflammation and fibrosis in different tissues [ 153 , 154 , 155 ]. When their effect on the heart and blood vessels was specifically assessed, atorvastatin ameliorated radiation-induced cardiac fibrosis, prevented vascular damage, reduced endothelial cell apoptosis, and promoted the healing of the radioactive injuries [ 124 , 156 , 157 ].…”