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Resveratrol increases the body’s resistance to stress

Zhigacheva I.V., Krikunova N.I., Mil E.M.

N.M. Emanuel Institute of Biochemical Physics of the Russian Academy of Sciences, 4, str. Kosygin, Moscow, 119334, Russia, phone: +7(495)939-74-09, fax: +7(499)137-41-01 e-mail: zhigacheva@mail.ru

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenolic compound with a stilbene structure. It has antioxidant and anti-inflammatory properties. The main target for resveratrol (RV) is mitochondria. The exact mechanism of the influence of RV on the functional state of mitochondria is not yet known. Therefore, the purpose of the study was to study the effect of resveratrol on the functional state of liver mitochondria under stress conditions.

Using the model of mitochondrial “aging” (incubation of mitochondria in a hypotonic salt environment at room temperature), the effect of different concentrations of RV on the intensity of lipid peroxidation was studied. “Aging” of liver mitochondria led to the activation of LPO in mitochondrial membranes. At the same time, the fluorescence intensity of LPO products in mitochondrial membranes increased 2-3 times. The introduction of RV into the incubation medium reduced the fluorescence intensity of LPO products and had a dose dependence. RV in the concentration range from 10-5 - 10-14M reduced the fluorescence intensity of LPO products almost to control values, which could probably indicate that the drug has anti-stress properties, the presence of which was studied using models of acute hypobaric hypoxia (AHH).

AHH also led to a 1.5-3-fold increase in the fluorescence intensity of lipid peroxidation products in the membranes of mouse liver mitochondria.

At the same time, activation of LPO was accompanied by swelling of mitochondria and changes in the content of C18 and C20-22 fatty acids (FAs) in the total lipid fraction of mitochondrial membranes. The C18 FA unsaturation index decreased by 7.5%. At the same time, the ratio between (20:3ω6+20:5ω3)/22:6ω3 FAs under AHH conditions decreased from 0.23±0.02 to 0.13±0.01, which indicated a decrease in metabolism in the eicosanoid cycle.

Injection of 2 × 10-5 mol/kg resveratrol to animals for 5 days prevented changes in FA composition, activation of lipid peroxidation and swelling of mitochondria, which affected physiological indicators: RV increased life expectancy by 2.0-2.5 times and by 10-15% increased the survival of mice under various types of hypoxia.

It is assumed that the adaptogenic properties of resveratrol may be due to the prevention of lipid peroxidation in mitochondrial membranes, which probably affected the functional state of these organelles, contributing to the preservation of the energy metabolism of the cell under stress.

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