THE NEUROPROTECTIVE EFFECT OF THE CARNOSINE IN A FOCAL CEREBRAL ISCHEMIA

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Issue: 
4
Year: 
2017

T.N. Fedorova
Dr.Sc. (Biol.), Research Center of Neurology (Moscow)
E-mail: tnf51@bk.ru
S.A. Gavrilova
Ph.D. (Biol.), Faculty of Fundamental Medicine, Lomonosov Moscow State University
M.P. Morozova
Ph.D. (Biol.), Faculty of Fundamental Medicine, Lomonosov Moscow State University
А.А. Devyatov
Laboratory Assistant Researcher, Research Center of Neurology (Moscow)
D.S. Berezhnoy
Ph.D. (Biol.), Research Center of Neurology (Moscow)
S.L. Stvolinsky
Dr.Sc. (Biol.), Research Center of Neurology (Moscow)

We have shown a direct neuroprotective effect of carnosine administered systemically at a daily dose of 50 mg/kg or 500 mg/kg, which was characterized by a significant decrease in the necrosis area by 27% and 39%, respectively, compared to animals treated with saline during a 72-hour period of permanent focal cerebral ischemia in rats. The evaluation of the oxidative status of animals after 72 h of a focal cerebral ischemia has demonstrated the following patterns. The brain tissue adjacent to the site of necrosis in the animals receiving saline showed an 88% increase in lipid hydroperoxides and a 35% reduction of the total antioxidant activity compared to intact animals. The systemic administration of the carnosine during the ischemia period, in a daily dose of 50 mg/kg or 500 mg/kg decreased a level of lipid hydroperoxides in the area adjacent to the focus of necrosis by 38,5% and 47%, respectively, compared to control animals and restored the total antioxidant activity of the brain tissue up to 100%-120% compared to intact animals. The focal cerebral ischemia was accompanied by a 2-fold decrease in the total antioxidant activity of the blood plasma of the animals compared to intact animals. The administration of carnosine at a daily dose of 500 mg/kg or 50 mg/kg restored the total antioxidant activity of the blood plasma to 100% and 82%, respectively. Our findings on the neuroprotective efficacy of low daily doses of carnosine in focal cerebral ischemia are a priority, as works of other researchers present data on the effectiveness of the carnosine in significantly higher doses (1000-2000 mg/kg body weight). Based on these data, we can assume that the neuroprotective effect of carnosine is due to its ability to prevent the development of oxidative damage in the ischemic penumbra zone and thereby prevent the impairment of the oxidative status of the whole organism.

Keywords: 
focal ischemia of the Brain
oxidative stress
carnosine
neuroprotection
antioxidative status.

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