Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P16104 (H2AX)
 3,930 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Pravastatin reduces radiation-induced damage in normal tissues. 2856 65