Изучение механизмов токсического действия уабаина на культуру клеток мозжечка крысы

Both endogenous and exogenous cardiotonic steroids (CTS), specific inhibitors of Na,K-ATPase, can evoke different physiological responses in the central nervous system by influencing synaptic transmission and intracellular signal cascades. In addition, they might participate in the development of neurodegenerative processes in the central nervous system. The toxicity of CTS for neurons has been shown earlier, but it has not been sufficiently characterized, and the mechanism of neuronal death has not been described in detail. In the present study it was shown that the viability of the primary cell culture of rat cerebellum under the action of 10 pM ouabain already decreases at 12 h of incubation and does not further decrease after 24 and 48 h of incubation, which suggests that this is a fast process, presumably apoptotic. At 12 h of incubation, the action of both toxic (10 pM) and nontoxic (1 pM) concentrations of ouabain leads to a shift in the ratio of apoptosis regulating proteins of the Bcl-2 family towards proapoptotic ones. At the same time, reducing the time of incubation of cells with 10 pM ouabain, but not with 1 pM ouabain, to 3 hours also leads to a decrease in the ratios of antiapoptotic proteins Bcl-2 and Bcl-xL to proapoptotic Bax and Bak, respectively, which indicates a fast development of apoptotic processes in response to ouabain neurotoxicity. Thus, it can be assumed that the effect of toxic concentrations of ouabain which cause neuronal death, is carried out through the mechanism of the mitochondrial apoptotic pathway.Изучены механизмы нейротоксического действия специфического ингибитора Na, К-АТФазы кардиотонического стероида уабаина. Показано, что уабаин в концентрации более 1 мкМ вызывает снижение жизнеспособности первичной культуры клеток мозжечка крысы при 12 ч инкубации; после 24 ч дальнейшее снижение жизнеспособности не наблюдается. При этом токсичные концентрации уабаина вызывают снижение отношения антиапоптотических белков семейства Bcl-2 к проапоптотическим

Carnosine as an effective neuroprotector in brain pathology and potential neuromodulator in normal conditions

Carnosine (b-alanyl-l-histidine) is an endogenous dipeptide widely distributed in excitable tissues, such as muscle and neural tissues—though in minor concentrations in the latter. Multiple benefits have been attributed to carnosine: direct and indirect antioxidant effect, antiglycating, metal-chelating, chaperone and pH-buffering activity. Thus, carnosine turns out to be a multipotent protector against oxidative damage. However, the role of carnosine in the brain remains unclear. The key aspects concerning carnosine in the brain reviewed are as follows: its concentration and bioavailability, mechanisms of action in neuronal and glial cells, beneficial effects in human studies. Recent literature data and the results of our own research are summarized here. This review covers studies of carnosine effects on both in vitro and in vivo models of cerebral damage, such as neurodegenerative disorders and ischemic injuries and the data on its physiological actions on neuronal signaling and cerebral functions. Besides its antioxidant and homeostatic properties, new potential roles of carnosine in the brain are discussed. © 2018, Springer-Verlag GmbH Austria, part of Springer Nature

Lipoylcarnosine: Synthesis, Study of Physico-Chemical and Antioxidant Properties, Biological Activity

Abstract—: Synthesis of lipoylcarnosine (LipС), a conjugated molecule based on two natural antioxidants, carnosine and α-lipoic acid, is described and its physico-chemical, antioxidant properties and biological activity are characterized. According to reversed-phase HPLC with a UV detector, purity of the final product was 89.3%. The individuality of the obtained sodium salt of LipС was confirmed by tandem HPLC-mass spectrometry. LipC demonstrated high resistance to hydrolysis with serum carnosinase. The antioxidant activity of LipC evaluated by the reaction with the formation of thiobarbituric acid reacting substances and kinetic parameters of iron-induced chemiluminescence was higher than that of carnosine and lipoic acid. LipC did not affect viability of SH-SY5Y human neuroblastoma cells, differentiated to the dopaminergic phenotype, at concentrations not exceeding 5 mM. In the concentration range of 0.1–0.25 mM LipC protected neuronal cells against 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity. © 2018, Pleiades Publishing, Ltd

Lipoilcarnosine: Synthesis, study of physico-chemical and antioxidant properties, biological activity

Synthesis of lipoilcarnosine (LipC) - a conjugated molecule based on two natural antioxidants, carnosine and a-lipoic acid, is described. Its physico-chemical, antioxidant properties and biological activity are characterized. According to reversed-phase HPLC with a UV detector, purity of the final product was 89.3%. The individuality of the obtained sodium salt of LipC was confirmed by tandem HPLC-mass spectrometry. High resistance of LipC to hydrolysis with serum carnosinase was demonstrated. The antioxidant activity of LipC measured by reaction with the formation of thiobarbituric acid reacting substances and kinetic parameters of iron-induced chemiluminescence was higher than that of carnosine and lipoic acid. LipC did not affect viability of SH-SY5Y human neuroblastoma culture cells, differentiated towards the dopaminergic type, at concentrations not exceeding 5 mM. At the concentration range of 0.1-0.25 mM LipC protected neuronal cells against 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity. © 2018 Russian Academy of Medical Sciences. All rights reserved

Lipoilcarnosine: Synthesis, study of physico-chemical and antioxidant properties, biological activity

Synthesis of lipoilcarnosine (LipC) - a conjugated molecule based on two natural antioxidants, carnosine and a-lipoic acid, is described. Its physico-chemical, antioxidant properties and biological activity are characterized. According to reversed-phase HPLC with a UV detector, purity of the final product was 89.3%. The individuality of the obtained sodium salt of LipC was confirmed by tandem HPLC-mass spectrometry. High resistance of LipC to hydrolysis with serum carnosinase was demonstrated. The antioxidant activity of LipC measured by reaction with the formation of thiobarbituric acid reacting substances and kinetic parameters of iron-induced chemiluminescence was higher than that of carnosine and lipoic acid. LipC did not affect viability of SH-SY5Y human neuroblastoma culture cells, differentiated towards the dopaminergic type, at concentrations not exceeding 5 mM. At the concentration range of 0.1-0.25 mM LipC protected neuronal cells against 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity. © 2018 Russian Academy of Medical Sciences. All rights reserved