Radioprotective Potential of Sulindac Sulfide to Prevent DNA Damage Due to Ionizing Radiation
Autor: | Nabizadeh Haghighi F, Mehdi Ansari, Rezaeifar M, Seyedeh Atekeh Torabizadeh, Ali Jomehzadeh |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Pharmacology chemistry.chemical_classification Reactive oxygen species biology DNA damage Radioprotective Agent Pharmaceutical Science medicine.disease_cause Malondialdehyde Molecular biology Lipid peroxidation Superoxide dismutase 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine chemistry 030220 oncology & carcinogenesis Drug Discovery medicine biology.protein Genotoxicity Oxidative stress |
Zdroj: | Drug Design, Development and Therapy. 13:4127-4134 |
ISSN: | 1177-8881 |
DOI: | 10.2147/dddt.s218022 |
Popis: | Introduction: The ionizing radiation exposure of the normal cell causes damage to DNA, which leads to cell dysfunction or even cell death. However, it is necessary to identify new radio protectives in order to protect normal cells. Sulindac sulfide (SS) is a metabolite of sulindac (a non-steroidal anti-inflammatory drug) known as a cyclooxygenase inhibitor. Free radicals and reactive oxygen species are generated in the IR-exposed cells. Also, the induced inflammation process causes damage in DNA. Purpose In this research, the radioprotective effect of SS was investigated against genotoxicity and lipid peroxidation induced by ionizing radiation in the human blood lymphocytes. Methods In this study, the human blood samples were pretreated with SS at different concentrations (10, 25, 50, 100 and 250 μM) and then were exposed to IR at a dose of 1.5 Gy. The micronucleus (MN) assay was used to indicate the radioprotective effects of SS on exposed cells. Total antioxidant activity of the SS was measured by using FRAP and DPPH assay. Also, the malondialdehyde (MDA) levels and the activity of superoxide dismutase (SOD) on the exposed cells were evaluated. Results It was found that SS decreased the percentage of MN induced by IR in exposed cells. Maximum reduction in the frequency of MN was observed at 250 μM of SS (87%) that provides the highest degree of protection against IR. On the other hand, pretreatment at 250 μM of SS inhibited IR-induced oxidative stress, which led to a decrease in the MN frequencies and MDA levels, while SOD activity showed an increase in the exposed cells. Conclusion It could be concluded that SS as a good radioprotective agent protects the human normal cells against the oxidative stress and genetic damage induced by IR. |
Databáze: | OpenAIRE |
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