advertisement
Abstract #24755 Published in IGR 11-4
Mitochondria-targeted rechargeable antioxidant SkQ1 prevents senescence in mammals
Skulachev VFEBS Journal 2009; 276 35-36
Cationic derivative of plastoquinone SkQ1 was synthesized and tested on BLM, mitochondria, cells and organisms. It is found that SkQ1 penetrates BLM and accumulates in mitochondria electrophoretically and due to high distribution coefficient (DC) in lipid/water systems. Assuming electric potential on plasma membrane and inner mitochondrial membrane as 60 and 180 mV respectively and DC = 13,000:1, one can predict that SkQ1 can accumulate in inner leaflet of inner mitochondrial membrane up to 130 min times. In mitochondria, 0.1 nM SkQ1 is shown to prevent lipid peroxidation accompanying aging of mitochondria in vitro. In cell cultures, SkQR1 specifically stains mitochondria and arrests ROS-induced apoptosis. SkQ1 increases the median lifespan of podospora, ceriodaphnia, drosophila and mouse (in the latter case, by factor 2). In mammals, the effect of SkQ1 on aging is accompanied by inhibition of development of cataract, retinopathy, glaucoma, balding, canities, osteoporosis, involution of thymus, hypothermia, torpor, chromosome aberrations, peroxidation of lipids and proteins, etc. With drops containing 250 nM SkQ1, vision is restored to 67 of 89 animals (dogs, cats, and horses) that became blind because of retinopathies. Moreover, the SkQ1 pretreatment of rats decreases the ROS- or ischemia-induced heart arrhythmia. SkQs strongly reduce damaged area in myocardial infarction or stroke and prevents death of animals from kidney ischemia. In mice without p53, 5 nmol SkQ1/kg x day inhibit appearance of lymphomas to the same degree as million-fold higher dose of conventional antioxidant NAC. Thus, SkQ1 looks promising as tool to treat senescence and age-related diseases.
V. Skulachev. Belozersky Institute, Bioenergetics, MoscowRussian Federation.
Classification:
15 Miscellaneous
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
