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Exp Ther Med. 2017 May;13(5):1765-1772. doi: 10.3892/etm.2017.4192. Epub 2017 Mar 8.

Pravastatin reduces radiation-induced damage in normal tissues.

Author information

1
Department of Radiology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
2
Department of Thoracic Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
3
Department of Pharmacy, Hyogo College of Medicine Sasayama Medical Center, Sasayama, Hyogo 669-2321, Japan.
4
Department of Radiological Technology, Hyogo College of Medicine College Hospital, Nishinomiya, Hyogo 663-8501, Japan.
5
Department of Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.

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.

KEYWORDS:

3-hyrdoxyl-3-methyl-glutaryl-conenzyme A reductase; DNA damage response; DNA double-strand breaks; mesothelioma; pravastatin; radioprotectant; radiotherapy; statin

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