Evaluation of the Protective Effect of Ademetionine, Cytoflavin, and Dihydroquercetetine on Blood Enzymes Activity in Ra
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the Protective Effect of Ademetionine, Cytoflavin, and Dihydroquercetetine on Blood Enzymes Activity in Rats Treated with High Doses of Sodium Valproate L. V. Okhremchuk1, I. Zh. Seminskii1, M. A. Darenskaya2, L. A. Grebenkina2, L. I. Kolesnikova2, and S. I. Kolesnikov2
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 170, No. 8, pp. 178-182, August, 2020 Original article submitted April 30, 2020 We evaluated the protective effect of ademetionine, cytoflavin, and dihydroquercetin on activity of serum enzymes in rats treated with high doses of sodium valproate for 28 days. Ademetionine and cytoflavin produced the greatest protective effect, the effect of dihydroquercetin was less pronounced. In rats treated with ademetionine, AST activity decreased as soon as on day 7 and remained at this level until the end of the experiment; ALT, alkaline phosphatase, and γ-glutamyl transferase activities decreased on days 21 and 28 of the study. Cytoflavin produced similar effects, the effect of dihydroquercetin was observed on days 21 and 28 for AST, ALT, alkaline phosphatase and on day 28 for γ-glutamyl transferase. These results substantiate the use of hepatoprotective drugs in case of long-term treatment with anticonvulsants in patients with epilepsy. Key Words: rats; sodium valproate; ademetionine; cytoflavin; dihydroquercetin Patients with epilepsy require long-term, sometimes for lifelong therapy with anticonvulsants. However, these drugs in addition to their direct positive effects can produce a wide range of negative side effects leading to systemic and mental disorders [8]. Among negative consequences, the increase in convulsive activity of the brain due to increased excitability of neurons is of particular importance, because it reduces the effectiveness of treatment and leads to the development of functional tolerance to drugs [8,15]. Anticonvulsant sodium valproate (SV) is used in the treatment of patients with epilepsy of different ages [15]. The mechanisms of action of SV include the effect on the GABA levels, blockade of sodium channels, and inhibition of histone deacetylases [12]. The most serious adverse reactions to SV are impairment of the functions of the liver and pancreas, as 1 Irkutsk State Medical University, Ministry of Health of the Russian Federation, Irkutsk, Russa; 2Research Centre for Family Health and Human Reproduction Problems, Irkutsk, Russia. Address for correspondence: [email protected]. M. A. Darenskaya
well as blood coagulation disturbances [2]. There are studies indicating multiple excess of SV dosage due to development of tolerance and the absence of desirable effect, which necessitate experimental evaluation of the effect of high doses of SV [12]. The development of numerous systemic disorders during long-term therapy with anticonvulsants determines advisability of prescribing drugs with hepatoprotective, antioxidant, and antihypoxic activity in the complex treatment of epilepsy. Active search for drugs that meet these requirements is in progress [7,13]. Th
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