The Ability of the Nitric Oxide Synthases Inhibitor T1023 to Selectively Protect the Non-Malignant Tissues
Previously, we showed that a nitric oxide synthase (NOS) inhibitor, compound T1023, induces transient hypoxia and prevents acute radiation syndrome (ARS) in mice. Significant efficacy (according to various tests, dose modifying factor (DMF)—1.6–1.9 against H-ARS/G-ARS) and safety in radioprotective...
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2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/17/9340 |
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| author | Marina Filimonova Alina Saburova Victoria Makarchuk Ljudmila Shevchenko Valentina Surinova Vadim Yuzhakov Nina Yakovleva Larisa Sevankaeva Vyacheslav Saburov Sergey Koryakin Petr Shegay Andrey Kaprin Sergey Ivanov Alexander Filimonov |
| author_facet | Marina Filimonova Alina Saburova Victoria Makarchuk Ljudmila Shevchenko Valentina Surinova Vadim Yuzhakov Nina Yakovleva Larisa Sevankaeva Vyacheslav Saburov Sergey Koryakin Petr Shegay Andrey Kaprin Sergey Ivanov Alexander Filimonov |
| author_sort | Marina Filimonova |
| collection | DOAJ |
| description | Previously, we showed that a nitric oxide synthase (NOS) inhibitor, compound T1023, induces transient hypoxia and prevents acute radiation syndrome (ARS) in mice. Significant efficacy (according to various tests, dose modifying factor (DMF)—1.6–1.9 against H-ARS/G-ARS) and safety in radioprotective doses (1/5–1/4 LD10) became the reason for testing its ability to prevent complications of tumor radiation therapy (RT). Research methods included studying T1023 effects on skin acute radiation reactions (RSR) in rats and mice without tumors and in tumor-bearing animals. The effects were evaluated using clinical, morphological and histological techniques as well as RTOG classification. T1023 administration prior to irradiation significantly limited the severity of acute RSR. This was due to a decrease in radiation alteration of the skin and underlying tissues, and the preservation of the functional activity of cell populations that are critical in the pathogenesis of radiation burn. The DMF values for T1023 for skin protection were 1.4–1.7. Moreover, its radioprotective effect was fully selective to normal tissues in RT models of solid tumors—T1023 reduced the severity of acute RSR and did not modify the antitumor effects of γ-radiation. The results indicate that T1023 can selectively protect the non-malignant tissues against γ-radiation due to hypoxic mechanism of action and potentiate opportunities of NOS inhibitors in RT complications prevention. |
| first_indexed | 2024-03-10T08:10:59Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:10:59Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9a3df3906d554792b38d19b1caf0cab42023-11-22T10:41:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012217934010.3390/ijms22179340The Ability of the Nitric Oxide Synthases Inhibitor T1023 to Selectively Protect the Non-Malignant TissuesMarina Filimonova0Alina Saburova1Victoria Makarchuk2Ljudmila Shevchenko3Valentina Surinova4Vadim Yuzhakov5Nina Yakovleva6Larisa Sevankaeva7Vyacheslav Saburov8Sergey Koryakin9Petr Shegay10Andrey Kaprin11Sergey Ivanov12Alexander Filimonov13A. Tsyb Medical Radiological Research Center—Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, 249036 Obninsk, RussiaA. Tsyb Medical Radiological Research Center—Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, 249036 Obninsk, RussiaA. Tsyb Medical Radiological Research Center—Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, 249036 Obninsk, RussiaA. Tsyb Medical Radiological Research Center—Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, 249036 Obninsk, RussiaA. Tsyb Medical Radiological Research Center—Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, 249036 Obninsk, RussiaA. Tsyb Medical Radiological Research Center—Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, 249036 Obninsk, RussiaA. Tsyb Medical Radiological Research Center—Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, 249036 Obninsk, RussiaA. Tsyb Medical Radiological Research Center—Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, 249036 Obninsk, RussiaA. Tsyb Medical Radiological Research Center—Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, 249036 Obninsk, RussiaA. Tsyb Medical Radiological Research Center—Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, 249036 Obninsk, RussiaNational Medical Research Radiological Center of the Ministry of Health of the Russian Federation, 249036 Obninsk, RussiaNational Medical Research Radiological Center of the Ministry of Health of the Russian Federation, 249036 Obninsk, RussiaA. Tsyb Medical Radiological Research Center—Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, 249036 Obninsk, RussiaA. Tsyb Medical Radiological Research Center—Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, 249036 Obninsk, RussiaPreviously, we showed that a nitric oxide synthase (NOS) inhibitor, compound T1023, induces transient hypoxia and prevents acute radiation syndrome (ARS) in mice. Significant efficacy (according to various tests, dose modifying factor (DMF)—1.6–1.9 against H-ARS/G-ARS) and safety in radioprotective doses (1/5–1/4 LD10) became the reason for testing its ability to prevent complications of tumor radiation therapy (RT). Research methods included studying T1023 effects on skin acute radiation reactions (RSR) in rats and mice without tumors and in tumor-bearing animals. The effects were evaluated using clinical, morphological and histological techniques as well as RTOG classification. T1023 administration prior to irradiation significantly limited the severity of acute RSR. This was due to a decrease in radiation alteration of the skin and underlying tissues, and the preservation of the functional activity of cell populations that are critical in the pathogenesis of radiation burn. The DMF values for T1023 for skin protection were 1.4–1.7. Moreover, its radioprotective effect was fully selective to normal tissues in RT models of solid tumors—T1023 reduced the severity of acute RSR and did not modify the antitumor effects of γ-radiation. The results indicate that T1023 can selectively protect the non-malignant tissues against γ-radiation due to hypoxic mechanism of action and potentiate opportunities of NOS inhibitors in RT complications prevention.https://www.mdpi.com/1422-0067/22/17/9340nitric oxide synthase inhibitorradiotherapyradiation-induced tissue toxicityselective radiation protection |
| spellingShingle | Marina Filimonova Alina Saburova Victoria Makarchuk Ljudmila Shevchenko Valentina Surinova Vadim Yuzhakov Nina Yakovleva Larisa Sevankaeva Vyacheslav Saburov Sergey Koryakin Petr Shegay Andrey Kaprin Sergey Ivanov Alexander Filimonov The Ability of the Nitric Oxide Synthases Inhibitor T1023 to Selectively Protect the Non-Malignant Tissues International Journal of Molecular Sciences nitric oxide synthase inhibitor radiotherapy radiation-induced tissue toxicity selective radiation protection |
| title | The Ability of the Nitric Oxide Synthases Inhibitor T1023 to Selectively Protect the Non-Malignant Tissues |
| title_full | The Ability of the Nitric Oxide Synthases Inhibitor T1023 to Selectively Protect the Non-Malignant Tissues |
| title_fullStr | The Ability of the Nitric Oxide Synthases Inhibitor T1023 to Selectively Protect the Non-Malignant Tissues |
| title_full_unstemmed | The Ability of the Nitric Oxide Synthases Inhibitor T1023 to Selectively Protect the Non-Malignant Tissues |
| title_short | The Ability of the Nitric Oxide Synthases Inhibitor T1023 to Selectively Protect the Non-Malignant Tissues |
| title_sort | ability of the nitric oxide synthases inhibitor t1023 to selectively protect the non malignant tissues |
| topic | nitric oxide synthase inhibitor radiotherapy radiation-induced tissue toxicity selective radiation protection |
| url | https://www.mdpi.com/1422-0067/22/17/9340 |
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