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Doi H, Matsumoto S, Odawara S, et al. Pravastatin reduces radiation-induced damage in normal tissues. Exp Ther Med. 2017;13(5):1765-1772doi: 10.3892/etm.2017.4192.
Doi, H., Matsumoto, S., Odawara, S., Shikata, T., Kitajima, K., Tanooka, M., Takada, Y., Tsujimura, T., Kamikonya, N., & Hirota, S. (2017). Pravastatin reduces radiation-induced damage in normal tissues. Experimental and therapeutic medicine, 13(5), 1765-1772. https://doi.org/10.3892/etm.2017.4192
Doi, Hiroshi, et al. "Pravastatin reduces radiation-induced damage in normal tissues." Experimental and therapeutic medicine vol. 13,5 (2017): 1765-1772. doi: https://doi.org/10.3892/etm.2017.4192
Doi H, Matsumoto S, Odawara S, Shikata T, Kitajima K, Tanooka M, Takada Y, Tsujimura T, Kamikonya N, Hirota S. Pravastatin reduces radiation-induced damage in normal tissues. Exp Ther Med. 2017 May;13(5):1765-1772. doi: 10.3892/etm.2017.4192. Epub 2017 Mar 08. PMID: 28565765; PMCID: PMC5443166.
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Exp Ther Med. 2017 May;13(5):1765-1772. doi: 10.3892/etm.2017.4192. Epub 2017 Mar 08.

Pravastatin reduces radiation-induced damage in normal tissues.

Experimental and therapeutic medicine

Hiroshi Doi, Seiji Matsumoto, Soichi Odawara, Toshiyuki Shikata, Kazuhiro Kitajima, Masao Tanooka, Yasuhiro Takada, Tohru Tsujimura, Norihiko Kamikonya, Shozo Hirota

Affiliations

  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.

PMID: 28565765 PMCID: PMC5443166 DOI: 10.3892/etm.2017.4192

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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