NDLI: Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 2. Treatment of some ROS- and Age-related diseases (heart arrhythmia, heart infarctions, kidney ischemia, and stroke)

Content Provider	Springer Nature Link
Author	Bakeeva, L. E. Barskov, I. V. Egorov, M. V. Isaev, N. K. Kapelko, V. I. Kazachenko, A. V. Kirpatovsky, V. I. Kozlovsky, S. V. Lakomkin, V. L. Levina, S. B. Pisarenko, O. I. Plotnikov, E. Y. Sapruva, V. B. Serebryakova, L. I. Skulachev, M. V. Stelmashook, E. V. Studneva, I. M. Tskitishvili, O. V. Vasilyeva, A. K. Victorov, I. V. Zorov, D. B. Skulachev, V. P.
Copyright Year	2008
Abstract	Effects of 10-(6′-plastoquinonyl) decyltriphenylphosphonium (SkQ1) and 10-(6′-plastoquinonyl) decylrhod-amine 19 (SkQR1) on rat models of H2O2- and ischemia-induced heart arrhythmia, heart infarction, kidney ischemia, and stroke have been studied ex vivo and in vivo. In all the models listed, SkQ1 and/or SkQR1 showed pronounced protective effect. Supplementation of food with extremely low SkQ1 amount (down to 0.02 nmol SkQ1/kg per day for 3 weeks) was found to abolish the steady heart arrhythmia caused by perfusion of isolated rat heart with H2O2 or by ischemia/reperfusion. Higher SkQ1 (125–250 nmol/kg per day for 2–3 weeks) was found to decrease the heart infarction region induced by an in vivo ischemia/reperfusion and lowered the blood levels of lactate dehydrogenase and creatine kinase increasing as a result of ischemia/reperfusion. In single-kidney rats, ischemia/reperfusion of the kidney was shown to kill the majority of the animals in 2–4 days, whereas one injection of SkQ1 or SkQR1 (1 μmol/kg a day before ischemia) saved lives of almost all treated rats. Effect of SkQR1 was accompanied by decrease in ROS (reactive oxygen species) level in kidney cells as well as by partial or complete normalization of blood creatinine and of some other kidney-controlled parameters. On the other hand, this amount of SkQ1 (a SkQ derivative of lower membrane-penetrating ability than SkQR1) saved the life but failed to normalize ROS and creatinine levels. Such an effect indicates that death under conditions of partial kidney dysfunction is mediated by an organ of vital importance other than kidney, the organ in question being an SkQ1 target. In a model of compression brain ischemia/reperfusion, a single intraperitoneal injection of SkQR1 to a rat (1 μmol/kg a day before operation) effectively decreased the damaged brain area. SkQ1 was ineffective, most probably due to lower permeability of the blood-brain barrier to this compound.
Starting Page	1288
Ending Page	1299
Page Count	12
File Format	PDF
ISSN	00062979
Journal	Biochemistry (Moscow)
Volume Number	73
Issue Number	12
e-ISSN	16083040
Language	English
Publisher	SP MAIK Nauka/Interperiodica
Publisher Date	2009-01-08
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	mitochondria-targeted antioxidant plastoquinone arrhythmia heart kidney infarction stroke Biomedicine general Microbiology Bioorganic Chemistry Biochemistry
Content Type	Text
Resource Type	Article
Subject	Biochemistry Biophysics Geriatrics and Gerontology

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