Neuroprotective Effects of Mitochondria-Targeted Plastoquinone and Thymoquinone in a Rat Model of Brain Ischemia/Reperfusion Injury

Molecules

Denis N. Silachev¹  Egor Y. Plotnikov¹  Ljubava D. Zorova²  Irina B. Pevzner¹  Natalia V. Sumbatyan²  Galina A. Korshunova¹  Mikhail V. Gulyaev³  Yury A. Pirogov⁴  Vladimir P. Skulachev¹  Dmitry B. Zorov¹ 

[1] Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskye Gory, House 1, Building 40, 119992 Moscow, Russia; E-Mails:;Institute of Mitoengineering, Lomonosov Moscow State University, Leninskye Gory, House 1, Building 73A, 119992 Moscow, Russia; E-Mails:;Faculty of Fundamental Medicine, Lomonosov Moscow State University, Lomonosovsky Prospekt, House 31-5, 117192 Moscow, Russia; E-Mail:;Faculty of Physics, Lomonosov Moscow State University, Leninskye Gory, House 1, Building 2, 119992 Moscow, Russia; E-Mail:

关键词: brain ischemia;    mitochondria-targeted antioxidants;    plastoquinone;    thymoquinone;    mitochondria;   

DOI  :  10.3390/molecules200814487

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.