OXYS Rats as a Model of Senile Cataract

Kolosova, N. G.; Lebedev, P. A.; Айдагулова, С. В.; Morozkova, T. S.

doi:10.1023/b:bebm.0000010967.24302.78

Cited by 30 publications

(16 citation statements)

References 9 publications

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“…These mechanisms may also have to do with the reduced level of oxidative damage in tissues and organs. Previously we showed that agerelated accumulation of the lipid and protein oxidation levels were abolished by adding to the food of SkQ1 in the same as in the present study, a dose in tissues of Wistar and more significantly of OXYS rats [23].…”

Section: Discussionsupporting

confidence: 82%

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Behavioral Effects Induced by Mitochondria-Targeted Antioxidant SkQ1 in Wistar and Senescence-Accelerated OXYS Rats

Stefanova

Фурсова

Kolosova

2010

JAD

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Abstract. Mitochondrial dysfunction is involved in aging and in neurodegenerative diseases and, therefore, pharmacological agents that alleviate mitochondrial dysfunction are expected to have neuroprotective effects. Promising in this respect is mitochondrial-targeted antioxidant plastoquinonyl-decyl-triphenylphosphonium (SkQ1). We investigated the effects of SkQ1 (250 nmol SkQ1/kg × day with food) on behavior in the elevated plus-maze (EPM) and open field (OF) and on spatial memory in a Morris water maze (MWM) in middle-aged (12 mo) Wistar and senescence-accelerated OXYS rats. Given that changes in the behavior of OXYS rats may be associated with visual impairment, the condition of the retina and the lens was evaluated by ophthalmoscopy. 14-month-old as well as 3-month-old OXYS rats had considerably reduced activities in OF, increased anxiety in EPM, and manifested impaired learning abilities in the MWM in comparison with Wistar rats. SkQ1-treated rats of both strains displayed significantly higher locomotor and exploratory activity in the OF and less anxiety in the EPM compared to age-matched controls. SkQ1 significantly improved visual ability of the rats reducing the severity of the developed signs of retinopathy and cataract but had no impact on OXYS rat's spatial memory in the MWM. SkQ1-treated Wistar rats exhibited slower learning in the MWM task comparison to the control group. Thus, SkQ1 had beneficial effects on locomotor and exploratory functions of the rat brain. Nevertheless, SkQ1 did not alter learning performance in the MWM in OXYS rats and slightly reduced it in the Wistar strain, which may be associated with differences in redox homeostasis.

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Section: Discussionsupporting

confidence: 82%

“…In comparison, for MitoQ this value is less than 2 times [22]. According to our data, addition of the above-mentioned SkQ1 amounts to the food completely prevents development of cataract and retinopathy in OXYS rats [23,24] as well as the age-dependent decline of the immune system [25,26].…”

Section: Introductionmentioning

confidence: 45%

Behavioral Effects Induced by Mitochondria-Targeted Antioxidant SkQ1 in Wistar and Senescence-Accelerated OXYS Rats

Stefanova

Фурсова

Kolosova

2010

JAD

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“…The selection of this strain was initiated by R. I. Salganik at the Novosibirsk Institute of Cytology and Genetics [45]. A few months after birth, such age-related diseases as cataract and retinal dystrophy appeared in these animals [46][47][48]. N. G. Kolosova and colleagues in the same institute found that the development of these signs of aging was strongly decelerated by treatment with SkQ1 (50-250 nmol/kg per day with food).…”

Section: The First Results Of the Project: Skqs As Tools Against Oxidmentioning

confidence: 99%

A biochemical approach to the problem of aging: “Megaproject” on membrane-penetrating ions. The first results and prospects

2007

Biochemistry Moscow

168

119

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REVIEW 1385Abbreviations: ∆ψ) transmembrane electric potential; BLM) planar bilayer phospholipid membrane; C 12 TPP) dodecyl triphenylphosphonium; DMQ) demethoxyMitoQ; MitoQ) compound of ubiquinone and decyl triphenylphosphonium; ROS) reactive oxygen species; SkQ) compounds of plastoquinone or methylplastoquinone and decyl (or amyl) triphenylphosphonium, methylcarninite, or tributylammonium; SkQ1) compound of plastoquinone and decyl triphenylphosphonium (other SkQ derivatives are shown in Fig. 3 Abstract-Antioxidants specifically addressed to mitochondria have been studied for their ability to decelerate aging of organisms. For this purpose, a project has been established with participation of several research groups from Belozersky Institute of Physico-Chemical Biology and some other Russian research institutes as well as two groups from the USA and Sweden, with support by the "Mitotechnology" company founded by "RAInKo" company (O. V. Deripaska and Moscow State University). This paper summarizes the first results of the project and estimates its prospects. Within the framework of the project, antioxidants of a new type (SkQ) were synthesized comprising plastoquinone (an antioxidant moiety), a penetrating cation, and decane or pentane linker. Using planar bilayer phospholipid membranes, we selected SkQ derivatives with the highest penetrating ability, namely plastoquinonyl-decyl-triphenylphosphonium (SkQ1), plastoquinonyl-decylrhodamine 19 (SkQR1), and methylplastoquinonyl-decyl-triphenylphosphonium (SkQ3). Anti-and prooxidant properties of these substances and also of ubiquinone and ubiquinonyl-decyl-triphenylphosphonium (MitoQ) were tested on isolated mitochondria. Micromolar concentrations of cationic quinones are found to be very strong prooxidants, but in lower (submicromolar) concentrations they display antioxidant activity. The antioxidant activity decreases in the series SkQ1 = SkQR1 > SkQ3 > MitoQ, so the window between the anti-and prooxidant effects is smallest for MitoQ. SkQ1 is rapidly reduced by complexes I and II of the mitochondrial respiratory chain, i.e. it is a rechargeable antioxidant. Extremely low concentrations of SkQ1 and SkQR1 completely arrest the H 2 O 2 -induced apoptosis in human fibroblasts and HeLa cells (for SkQ1 C 1/2 = 1⋅10 -9 M). Higher concentrations of SkQ are required to block necrosis initiated by reactive oxygen species (ROS). In mice, SkQ1 decelerates the development of three types of accelerated aging (progeria) and also of normal aging, and this effect is especially demonstrative at early stages of aging. The same pattern is shown in invertebrates (drosophila and daphnia). In mammals, the effect of SkQs on aging is accompanied by inhibition of development of such age-related diseases as osteoporosis, involution of thymus, cataract, retinopathy, etc. SkQ1 manifests a strong therapeutic action on some already developed retinopathies, in particular, congenital retinal dysplasia. With drops containing 250 nM SkQ1, vision is recovered in 50 of 66 animals who became blind be...

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“…The OXYS strain of rats may be very useful as a model to study the role of ROS in the process of aging, since this strain is characterized by ROS overproduction or by increased sensitivity to free radicals, which forms the basis of premature aging, short lifespan, low fertility, and increased frequency of cancers and chronic diseases (cataracts, cardiomyopathy, etc.) [13,14,29,30].…”

Section: Discussionmentioning

confidence: 99%

Age‐associated changes in oxidative damage and the activity of antioxidant enzymes in rats with inherited overgeneration of free radicals

Синицына

Krysanova

Ищенко

et al. 2006

J Cellular Molecular Medi

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All higher organisms generate energy by aerobic respiration, a process that involves a stepwise fourelectron reduction of molecular oxygen to water.The partially reduced species that are produced as intermediates and by-products of aerobic respiration, including · O 2 -, H 2 O 2, and · OH, are potent oxidants attacking different cellular components including DNA of mitochondria and nuclei [1]. These oxidants also appear in cells through exposure to ionizing radiation and other agents that generate free radicals. A major target of reactive oxy- AbstractReactive oxygen species have been hypothesized to play an important role in the process of aging. To investigate the correlation between oxidative stress and accumulation of protein and DNA damage, we have compared the agedependent levels of protein carbonyl groups and the activities of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase in cytosol and mitochondrial extracts from liver cells of Wistar and OXYS rats. The latter strain is characterized by increased sensitivity to free radicals. Faster age-dependent increase in the level of protein carbonyl groups was found in OXYS as compared with Wistar rats. A complicated enzyme-specific pattern of age-dependent changes in the activities of antioxidant enzymes was observed. Long-term uptake of dietary supplements Mirtilene forte (extract from the fruits of Vaccinium myrtillus L.) or Adrusen zinco (vitamin E complex with zinc, copper, selenium and ω-3 polyunsaturated fatty acids) sharply decreased the level of protein oxidation in cytosol and mitochondrial extracts of hepatocytes of Wistar and of OXYS rats. Both dietary supplements increased the activity of catalase in the liver mitochondria of OXYS rats. Our results are in agreement with the shorter life-span of OXYS and with the mitochondrial theory of aging, which postulates that accumulation of DNA and protein lesions leads to mitochondrial dysfunction and accelerates the process of aging.

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OXYS Rats as a Model of Senile Cataract

Cited by 30 publications

References 9 publications

Behavioral Effects Induced by Mitochondria-Targeted Antioxidant SkQ1 in Wistar and Senescence-Accelerated OXYS Rats

Behavioral Effects Induced by Mitochondria-Targeted Antioxidant SkQ1 in Wistar and Senescence-Accelerated OXYS Rats

A biochemical approach to the problem of aging: “Megaproject” on membrane-penetrating ions. The first results and prospects

Age‐associated changes in oxidative damage and the activity of antioxidant enzymes in rats with inherited overgeneration of free radicals

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