Pravastatin reduces radiation-induced damage in normal tissues

Our plain-English summary of Pravastatin reduces radiation-induced damage in normal tissues, by H. Doi, S. Matsumoto, S. Odawara, et al (Experimental and Therapeutic Medicine, 2017).

The study

• Authors: H. Doi, S. Matsumoto, S. Odawara, T. Shikata, K. Kitajima, M. Tanooka, Y. Takada, T. Tsujimura, N. Kamikonya, S. Hirota
• Journal: Experimental and Therapeutic Medicine
• Published: 2017;13(5):1765-1772
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This was an animal experiment from Hyogo College of Medicine, Japan, testing whether pravastatin, a cholesterol drug, protects normal tissue from radiation. It did not study asbestos. Mesothelioma appeared only as a human mesothelioma cell line (NCI-H226) grown as tumors in mice. Mice received pravastatin, 30 mg/kg in drinking water, 24 and 4 hours before X-ray irradiation. Control mice received plain water. After 15 Gy, pravastatin-treated mice had more surviving intestinal crypts, but the difference was statistically significant only in the ileum (average 15.44 versus 6.41 in controls). After 2 Gy, the pravastatin group had significantly lower rates of cell death in all three parts of the small intestine. Markers of DNA breaks (ATM and gamma-H2AX) were also lower in that group. In the lung, cell death was lower, but the difference was not statistically significant (P=0.060). Pravastatin did not significantly change how mesothelioma tumors responded to radiation. The authors concluded that pravastatin protected intestine and lung tissue. They named the small number of animals as a limitation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment comparing irradiated mice given pravastatin with irradiated control mice given plain water, plus a mouse tumor (xenograft) experiment
• Who was studied: Male C57BL/6 J mice aged 7 to 8 weeks from Charles River Laboratories Japan, four mice per treatment group for the intestine and lung tests. For the tumor test, female nude mice carrying tumors grown from human mesothelioma cells (NCI-H226): 3 sham-irradiated without pravastatin, 3 sham-irradiated with pravastatin, 6 irradiated without pravastatin, and 6 irradiated with pravastatin. Hyogo College of Medicine, Japan.
• Exposure: Pravastatin 30 mg/kg body weight given by mouth in drinking water 24 and 4 hours before X-ray irradiation. Single radiation doses were 15 Gy total body (crypt survival), 2 Gy total body (intestinal cell death), 5 Gy total body (lung cell death), 20 Gy abdominal (survival) and 8 Gy to the tumors. No asbestos exposure was studied.
• Main results:
  • Viable intestinal crypts after 15 Gy (duodenum, jejunum, ileum): 4.84, 9.38 and 6.41 in the control group, and 6.41, 13.22 and 15.44 in the pravastatin group
  • The increase in viable crypts with pravastatin was statistically significant only in the ileum (P less than 0.0001)
  • Apoptotic index (share of dying cells per crypt) after 2 Gy (duodenum, jejunum, ileum): 0.19, 0.23 and 0.28 in the control group versus 0.08, 0.10 and 0.10 in the pravastatin group
  • Intestinal cell death was significantly lower in the pravastatin group in all examined parts of the intestine (P less than 0.0001)
  • Proportion of ATM-positive cells (a DNA-damage marker): 0.83 in the control group versus 0.69 in the pravastatin group (P less than 0.0001)
  • Proportion of gamma-H2AX-positive cells (a marker of DNA double-strand breaks): 0.91 in the control group versus 0.82 in the pravastatin group (P=0.0079)
  • After 20 Gy abdominal irradiation, pravastatin gave no significant improvement in acute gastrointestinal syndrome in a mouse survival assay (data not shown)
  • Lung cell death (TUNEL-positive cells per lobe) after 5 Gy: 4.26 in the control group versus 3.36 in the pravastatin group (P=0.060), a difference that was not statistically significant
  • In mice with mesothelioma xenograft tumors, tumor response to irradiation did not differ significantly between irradiation alone and irradiation with pravastatin (P=0.855)
• The authors' conclusion: The authors concluded that pravastatin protected normal intestine and lung tissues from radiation, that this was associated with fewer radiation-induced DNA double-strand breaks, and that pravastatin may increase the therapeutic index of radiotherapy
• Limitations the authors state:
  • A relatively small number of animals was used
  • The reduction in lung cell death was not statistically significant
  • The lung was examined at only one time point after irradiation
  • The mechanism was studied only by immunohistochemistry. Upstream DNA-damage responses, such as reactive oxygen species, and pravastatin's effect on the cell cycle remain unclear.

Topics

Medical terms in this study, explained in our Lexicon: Apoptosis, Immunohistochemistry, Mesothelioma.

Related studies

• A single intratracheal instillation of single-walled carbon nanotubes induced early lung fibrosis and subchronic tissue damage in mice — E.J. Park, J. Roh, et al. (2011)
• Can microwave radiation at high temperatures reduce the toxicity of fibrous crocidolite asbestos? — M. Gulumian, Z.L. Nkosibomvu, et al. (1997)
• Low-voltage chest CT: another way to reduce the radiation dose in asbestos-exposed patients — D. Macía-Suárez, E. Sánchez-Rodríguez, et al. (2017)
• Nucleosomes effectively shield DNA from radiation damage in living cells — F. Brambilla, J.M. Garcia-Manteiga, et al. (2020)
• Effects of Photon Radiation on DNA Damage, Cell Proliferation, Cell Survival, and Apoptosis of Murine and Human Mesothelioma Cell Lines — S. Keam, K.M. MacKinnon, et al. (2022)
• Prognostic and diagnostic role of PSA immunohistochemistry: A tissue microarray study on 21,000 normal and cancerous tissues — S. Bonk, M. Kluth, et al. (2019)

Browse more research in Experimental and Therapeutic Medicine, or return to medical research.