[Effect of precursors and modulators of coenzyme Q biosynthesis on the heart mitochondria function in aged rats].

Our research demonstrate that ageing leads to changes in activity of electron-transporting enzyme complexes in myocardial mitochondria of old rats and to increased sensitivity of mitochondrial permeability transition pore to inductors of its opening--Ca2+ and phenylarsine oxide. We also observed activation of lipid and protein free-radical peroxidation processes. Administration of a complex of biologically active substances that included precursors and modulators of coenzyme Q biosynthesis (alpha-tocopherol acetate, 4-hydroxybenzoic acid, and methionine) we observed the increase in coenzyme Q content, correction of functional activity of mitochondrial electron-transport chain enzyme complexes, the decrease in intensivity of lipid and protein free-radical peroxidation in the heart and the decrease in sensitivity of mitochondrial permeability transition pore to inductors of its opening. This complex may be used to treat mitochondrial dysfunction under numerous pathologies of cardiovascular system, as well as in ageing.

[Cardioprotective action of coenzyme Q in conditions of its endogenous synthesis activation in cardiac ischemia-reperfusion in old rats].

The changes of functional state isolated by Lanhendorf old rat hearts with low content of ubiqinone--coenzyme Q (CoQ) under activation of it endogenous synthesis through administration of precursors--4-hydroxybenzoic acid, methionine and modulator vitamin E were studied. The activation of ubiqinone biosynthesis contribute to cardioprotective effect due to reduce the degree of the ischemia-reperfusion injury in old rat heart, namely the restoration of myocardial contractile function and coronary flow as well as decrease the end diastolic pressure and oxygen cost of the heart compared with control group of the animals during ischemia-reperfusion. Thus the results allow to conclude that the activation of KoQ biosynthesis under administration of it precursors has protective effect in the development of the heart postreperfusion damages in aging.

[Expression of UCP3 and the sensitivity of mitochondrial permeability transition pore opening to Ca2+ in old rat heart under activation of biosynthesis of coenzyme Q].

The expression of mitochondrial uncoupling protein 3 (UCP3), as well as the sensitivity of mitochondrial permeability transition pore opening (MPTP) to Ca2+ (10(-4) mol/l) in old rat heart under activation in vivo of ubiquinone synthesis--coenzyme Q, (CoQ) via administration of the precursors (4-hydroxybenzoic acid, aminoacid methionine and modulator vitamin E) were studied. It was shown that the expression level of UCP3 decreased by 63% in old rats compared to adult rats and this was accompanied by an increased sensitivity of the MPT to calcium. Under activation of endogenous synthesis of CoQ it was observed almost complete restoration of UCP3 expression in old rat heart and a decrease in the sensitivity of the MPTP opening to Ca2+. In mitochondria from old rat hearts we noted an increased content of the superoxide (O2) and hydroxyl (OH) radicals and of the stable metabolite of active oxygen species hydrogen peroxide (H2O2), as compared to those in adult animals. Following activation of endogenous synthesis of CoQ in old rat heart mitochondria it was observed a decreased content of H2O2, and the tendency for decreasing the levels of the radicals O2 and MOH. The results obtained allowed to conclude that the CoQ-dependent restoration of the UCP3 levels in old rat heart and antioxidant/cardioprotective effects of CoQ related to the MPTP opening inhibition can reduce the oxidative stress and thus prevent the manifestation of mitochondrial dysfunction in aging heart. We suggest that UCP3 is not involved in the increase of the passive H-conductance through the inner mitochondrial membrane in the aging heart, and that CoQ as a factor of respiratory chain could be an important endogenous regulator of the uncoupling proteins, in particular UCP3, in the heart.

[An increased sensitivity of the mitochondrial permeability transition pore to calcium in the heart of rats with chronic deficiency of nigrostriatal dopamine].

We studied the sensitivity of mitochondrial permeability transition pore (MPTP) opening to natural inductors--Ca2+ ions in the rat heart mitochondria with chronic deficiency of nigrostriatal dopamine caused by an injection of selective neurotoxin 6-hydroxidofamine in an ascending lateral bundle of the forebrain. MPTP-opening was determined specrophotometrically (lamda=520 nm) by a decrease in an optical density resulting from mitochondrial swelling. It has been shown that the rat heart mitochondria with chronic deficiency of nigrostriatal dopamine are more sensitive to Ca2+ in its physiological concentration (10(-7) mol/l) and overload (10(-6) - 10(-4) mol/l) in comparison to control animals. Thus, obtained results lead to a conclusion that an increased sensitivity of the mitochondrial permeability transition pore to calcium and mitochondrial membrane permeability may be one of the causes previously reported of disturbance in contractile function of the rat heart with chronic deficiency of nigrostriatal dopamine.

[In vivo effect of precursors of ubiquinone biosynthesis on sensitivity of mitochondrial permeability transition pore in the heart of old rats].

This research work is devoted to study of the sensitivity of mitochondrial permeability transition pore (MPTP) opening to its inductors--ions Ca2+ (10(-4) mol/l) and oxidant phenylarsine oxide (10(-4) mol/l) and content of ubiquinone (coenzyme Q, CoQ) and vitamin E in heart mitochondria of adult, old (control) and old rats under administration of precursors an modulator of CoQ biosynthesis--4-hydroxybenzoic acid, methionine and modulator of CoQ biosynthesis, namely vitamin E. The results of our research demonstrate that administration of complex of biologically active substances, which are precursors and modulators of CoQ biosynthesis, leads to decrease in the sensitivity of MPTP opening to its inductors and increase of CoQ and vitamin E content in old rats heart mitochondria. Therefore the results obtained lead to a conclusion that increase of CoQ content due to administration of precursors and modulator of its biosynthesis is an effective way in the inhibition of MPTP opening. This approach as well as application of CoQ-containing medicals may be used for correction of mitochondrial dysfunction under various pathologies of cardiovascular system and in aging.