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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*

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