| Abstrakt: |
Abstract: Female mice of the outbred SHR strain, the inbred 129/Sv strain, and the high cancer rate transgenic HER-2/neu strain were given a mitochondria-targeted derivative of plastoquinone SkQ1 (10E (6′-plastoquinonyl)-decyltriphenylphosphonium) in drinking water from the age of two months at doses of 0.5–2500 nmol/kg of body weight per day. The animals of the control groups received drinking water without the drug. We evaluated the age-related changes in the body weight and temperature, the amount of consumed drinking water and food, estrous function, locomotor activity in the “open field” test, muscle strength and fatigability in the wire suspension test, and anxiety in the elevated plus maze, as well as indices of lifespan and carcinogenesis. We did not observe substantial differences in the body weight, temperature, and amount of consumed drinking water and food between the animals of the experimental and control groups. In SHR mice treated with SkQ1, we observed a tendency toward the inhibition of age-related disturbances of the estrous function. The drug did not influence estrous function in the transgenic or inbred animals. SkQ1 substantially decreased locomotor activity and exercise tolerance in 129/Sv and SHR mice and did not affect anxiety in SHR mice. We observed a tendency toward the inhibition of external indices of aging in SHR mice treated with various doses of SkQ1. In SHR mice, administration of SkQ1 at doses of 0.5–50 nmol/kg was associated with an elevation of the main parameters of the lifespan (LS), including the mean LS value, the mean LS value of the last 10%, the median value, and the maximum LS value. It did not influence the LS parameters in the female 129/Sv and HER-2/neu mice. In three mice strains studied, SkQ1 treatment at all doses did not substantially affect spontaneous carcinogenesis; however, it significantly decreased mortality in SHR mice from nontumor-related pathologies. Our data support the hypothesis on the geroprotective properties of SkQ1 and a lack of general toxic and carcinogenic activity after long-term treatment with it. |
Full text from SpringerLink