Neuroprotective Effects of Mitochondria-Targeted Plastoquinone and Thymoquinone in a Rat Model of Brain Ischemia/Reperfusion Injury
We explored the neuroprotective properties of natural plant-derived antioxidants plastoquinone and thymoquinone (2-demethylplastoquinone derivative) modified to be specifically accumulated in mitochondria. The modification was performed through chemical conjugation of the quinones with penetrating c...
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MDPI AG
2015-08-01
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| Series: | Molecules |
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| author | Denis N. Silachev Egor Y. Plotnikov Ljubava D. Zorova Irina B. Pevzner Natalia V. Sumbatyan Galina A. Korshunova Mikhail V. Gulyaev Yury A. Pirogov Vladimir P. Skulachev Dmitry B. Zorov |
| author_facet | Denis N. Silachev Egor Y. Plotnikov Ljubava D. Zorova Irina B. Pevzner Natalia V. Sumbatyan Galina A. Korshunova Mikhail V. Gulyaev Yury A. Pirogov Vladimir P. Skulachev Dmitry B. Zorov |
| author_sort | Denis N. Silachev |
| collection | DOAJ |
| description | We explored the neuroprotective properties of natural plant-derived antioxidants plastoquinone and thymoquinone (2-demethylplastoquinone derivative) modified to be specifically accumulated in mitochondria. The modification was performed through chemical conjugation of the quinones with penetrating cations: Rhodamine 19 or tetraphenylphosphonium. Neuroprotective properties were evaluated in a model of middle cerebral artery occlusion. We demonstrate that the mitochondria-targeted compounds, introduced immediately after reperfusion, possess various neuroprotective potencies as judged by the lower brain damage and higher neurological status. Plastoquinone derivatives conjugated with rhodamine were the most efficient, and the least efficiency was shown by antioxidants conjugated with tetraphenylphosphonium. Antioxidants were administered intraperitoneally or intranasally with the latter demonstrating a high level of penetration into the brain tissue. The therapeutic effects of both ways of administration were similar. Long-term administration of antioxidants in low doses reduced the neurological deficit, but had no effect on the volume of brain damage. At present, cationic decylrhodamine derivatives of plastoquinone appear to be the most promising anti-ischemic mitochondria-targeted drugs of the quinone family. We suggest these antioxidants could be potentially used for a stroke treatment. |
| first_indexed | 2024-04-12T17:02:52Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-12T17:02:52Z |
| publishDate | 2015-08-01 |
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| series | Molecules |
| spelling | doaj.art-f8a7d86faa9a4f91b58f4b66e549e72b2022-12-22T03:24:02ZengMDPI AGMolecules1420-30492015-08-01208144871450310.3390/molecules200814487molecules200814487Neuroprotective Effects of Mitochondria-Targeted Plastoquinone and Thymoquinone in a Rat Model of Brain Ischemia/Reperfusion InjuryDenis N. Silachev0Egor Y. Plotnikov1Ljubava D. Zorova2Irina B. Pevzner3Natalia V. Sumbatyan4Galina A. Korshunova5Mikhail V. Gulyaev6Yury A. Pirogov7Vladimir P. Skulachev8Dmitry B. Zorov9Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskye Gory, House 1, Building 40, 119992 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskye Gory, House 1, Building 40, 119992 Moscow, RussiaInstitute of Mitoengineering, Lomonosov Moscow State University, Leninskye Gory, House 1, Building 73A, 119992 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskye Gory, House 1, Building 40, 119992 Moscow, RussiaInstitute of Mitoengineering, Lomonosov Moscow State University, Leninskye Gory, House 1, Building 73A, 119992 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskye Gory, House 1, Building 40, 119992 Moscow, RussiaFaculty of Fundamental Medicine, Lomonosov Moscow State University, Lomonosovsky Prospekt, House 31-5, 117192 Moscow, RussiaFaculty of Physics, Lomonosov Moscow State University, Leninskye Gory, House 1, Building 2, 119992 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskye Gory, House 1, Building 40, 119992 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskye Gory, House 1, Building 40, 119992 Moscow, RussiaWe explored the neuroprotective properties of natural plant-derived antioxidants plastoquinone and thymoquinone (2-demethylplastoquinone derivative) modified to be specifically accumulated in mitochondria. The modification was performed through chemical conjugation of the quinones with penetrating cations: Rhodamine 19 or tetraphenylphosphonium. Neuroprotective properties were evaluated in a model of middle cerebral artery occlusion. We demonstrate that the mitochondria-targeted compounds, introduced immediately after reperfusion, possess various neuroprotective potencies as judged by the lower brain damage and higher neurological status. Plastoquinone derivatives conjugated with rhodamine were the most efficient, and the least efficiency was shown by antioxidants conjugated with tetraphenylphosphonium. Antioxidants were administered intraperitoneally or intranasally with the latter demonstrating a high level of penetration into the brain tissue. The therapeutic effects of both ways of administration were similar. Long-term administration of antioxidants in low doses reduced the neurological deficit, but had no effect on the volume of brain damage. At present, cationic decylrhodamine derivatives of plastoquinone appear to be the most promising anti-ischemic mitochondria-targeted drugs of the quinone family. We suggest these antioxidants could be potentially used for a stroke treatment.http://www.mdpi.com/1420-3049/20/8/14487brain ischemiamitochondria-targeted antioxidantsplastoquinone, thymoquinonemitochondria |
| spellingShingle | Denis N. Silachev Egor Y. Plotnikov Ljubava D. Zorova Irina B. Pevzner Natalia V. Sumbatyan Galina A. Korshunova Mikhail V. Gulyaev Yury A. Pirogov Vladimir P. Skulachev Dmitry B. Zorov Neuroprotective Effects of Mitochondria-Targeted Plastoquinone and Thymoquinone in a Rat Model of Brain Ischemia/Reperfusion Injury Molecules brain ischemia mitochondria-targeted antioxidants plastoquinone, thymoquinone mitochondria |
| title | Neuroprotective Effects of Mitochondria-Targeted Plastoquinone and Thymoquinone in a Rat Model of Brain Ischemia/Reperfusion Injury |
| title_full | Neuroprotective Effects of Mitochondria-Targeted Plastoquinone and Thymoquinone in a Rat Model of Brain Ischemia/Reperfusion Injury |
| title_fullStr | Neuroprotective Effects of Mitochondria-Targeted Plastoquinone and Thymoquinone in a Rat Model of Brain Ischemia/Reperfusion Injury |
| title_full_unstemmed | Neuroprotective Effects of Mitochondria-Targeted Plastoquinone and Thymoquinone in a Rat Model of Brain Ischemia/Reperfusion Injury |
| title_short | Neuroprotective Effects of Mitochondria-Targeted Plastoquinone and Thymoquinone in a Rat Model of Brain Ischemia/Reperfusion Injury |
| title_sort | neuroprotective effects of mitochondria targeted plastoquinone and thymoquinone in a rat model of brain ischemia reperfusion injury |
| topic | brain ischemia mitochondria-targeted antioxidants plastoquinone, thymoquinone mitochondria |
| url | http://www.mdpi.com/1420-3049/20/8/14487 |
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