Abstract

New-Generation Skulachev Ions Exhibiting Nephroprotective and Neuroprotective Properties

E. Y. Plotnikov^1,2#, D. N. Silachev^1,2#, A. A. Chupyrkina^1,2, M. I. Danshina², S. S. Jankauskas², M. A. Morosanova^2,3, E. V. Stelmashook^2,4, A. K. Vasileva^1,2, E. S. Goryacheva^2,3, Y. A. Pirogov⁵, N. K. Isaev^1,2,4, and D. B. Zorov^1,2

¹Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia; fax: (495) 939-3181; E-mail: isaev@genebee.msu.su; zorov@genebee.msu.su

²Mitoengineering Research Institute, Lomonosov Moscow State University, 119992 Moscow, Russia

³Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991 Moscow, Russia

⁴Department of Brain Research, Neurology Research Center, Russian Academy of Medical Sciences, Pereulok Obukha 5, 105064 Moscow, Russia

⁵Training and Research Interfaculty Center of Magnetic Tomography and Spectroscopy, Lomonosov Moscow State University, 119991 Moscow, Russia

^# These authors contributed equally.

^* To whom correspondence should be addressed.

Received November 5, 2009
A mitochondria-targeted chimeric compound consisting of a rhodamine derivative linked to a plastoquinone molecule (10-(6′-plastoquinonyl)decylrhodamine, SkQR1) was studied under conditions of acute brain or kidney damage. A protective effect of this compound was demonstrated in a model of focal brain ischemia, rat kidney ischemia/reperfusion, myoglobinuria (rhabdomyolysis, or crush syndrome), and pyelonephritis. We found that a single intraperitoneal injection of SkQR1 diminishes the size of the ischemic zone in the brain and improves performance of a test characterizing neurological deficit in ischemic animals. Control substance not containing plastoquinone appeared to be not neuroprotective. The data show that SkQR1 is a nephroprotectant and neuroprotectant, which can be due to the antioxidative action of this Skulachev cation.
KEY WORDS: Skulachev ions, SkQ, SkQR1, kidney, oxidative stress, mitochondria-targeted antioxidants, mitochondria, rhabdomyolysis, pyelonephritis, brain ischemia, magnetic resonance tomography
DOI: 10.1134/S0006297910020045

New-Generation Skulachev Ions Exhibiting Nephroprotective and Neuroprotective Properties

E. Y. Plotnikov1,2#, D. N. Silachev1,2#, A. A. Chupyrkina1,2, M. I. Danshina2, S. S. Jankauskas2, M. A. Morosanova2,3, E. V. Stelmashook2,4, A. K. Vasileva1,2, E. S. Goryacheva2,3, Y. A. Pirogov5, N. K. Isaev1,2,4*, and D. B. Zorov1,2*

E. Y. Plotnikov^1,2#, D. N. Silachev^1,2#, A. A. Chupyrkina^1,2, M. I. Danshina², S. S. Jankauskas², M. A. Morosanova^2,3, E. V. Stelmashook^2,4, A. K. Vasileva^1,2, E. S. Goryacheva^2,3, Y. A. Pirogov⁵, N. K. Isaev^1,2,4, and D. B. Zorov^1,2