New-generation Skulachev ions exhibiting nephroprotective and neuroprotective properties.
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.
Plotnikov
E Y
EY
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russia.
Silachev
D N
DN
Chupyrkina
A A
AA
Danshina
M I
MI
Jankauskas
S S
SS
Morosanova
M A
MA
Stelmashook
E V
EV
Vasileva
A K
AK
Goryacheva
E S
ES
Pirogov
Y A
YA
Isaev
N K
NK
Zorov
D B
DB
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009212:Myoglobinuria / Q000378:metabolism / Q000503:physiopathology; D009422:Nervous System Diseases / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010971:Plastoquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D011704:Pyelonephritis / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D012235:Rhodamines / Q000494:pharmacology*
C534903:10-(6'-plastoquinonyl) decylrhodamine 19; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D012235:Rhodamines; D010971:Plastoquinone