Rro/antioxidant activity of a new pir-10 substance (pyrimidine derivative) under experimentally simulated focal cerebral iscemia in rats

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UDC: 
547.853: 615.225: 616.13
DOI: 
10.21668/health.risk/2019.1.11.eng
Authors: 

А.V. Voronkov, N.B. Shabanova

Organization: 

Pyatigorsk Medical and Pharmaceutical Institute, a branch of Volgograd State Medical University, The RF Public Healthcare Ministry, 11 Kalinina av., Pyatigorsk, 357532, Russian Federation

Abstract: 

The authors have performed a piece of research that focused on assessing anti-oxidant activity of PIR-10, a new pyrimidine derivative, as a risk factor causing disorders in the cerebral hemodynamics under experimentally simulated focal cerebral ischemia in rats. The experiment was accomplished on male Wistar rats with body weight equal to 220–240. 40 animals were distributed into 4 equal groups (n=10). The first group was made up of falsely operated animals; the second one was a negative control group; animals from both these groups were given a water suspension purified with TWEEN-80 in equivalent volumes. The third group included rats that were given a reference medication, namely Mexidol (emoxypine) (50 mg/kg). Animals from the fourth group were given an experimental substance with a laboratory cipher PIR-10 (50 mg/kg). All the examined objects were introduced intraperitoneally immediately after a surgery and during 3 days. Local cerebral ischemia was induced via coagulation of the left mesencephalic artery. All the manipulations with animals were performed under chloral hydrate narcosis (350 mg/kg). The performed research allowed to reveal that the given pathology caused an increase in lipid peroxidation products (diene conjugates (DC) and malonic dialdehyde (MDA)) with a simultaneous decrease in endogenous anti-oxidant protection (AOP) enzymes (superoxide dismutase, glutathione peroxidase, catalase). Mexidol application in a dose equal to 50 mg/kg allowed to correct these disorders due to an increase in antioxidant protection activity and a fall in concentrations of lipid peroxidation products. Introduction of the experimental substance PIR-10 also caused a decrease in DC and MDA concentrations but it didn't produce any effects on AOP system. Therefore, basing on the research results, we can assume that PIR-10 substance is a promising object for further research aimed at creating a medication with antioxidant properties that could allow to minimize epidemiologic risks related to cerebrovascular pathology.

Keywords: 
rats, cerebral ischemia, focal cerebral ischemia, antioxidant activity, lipid peroxidation, free radical oxidation, Mexidol, pyrimidine derivatives
Voronkov А.V., Shabanova N.B. Pro/antioxidant activity of a new PIR-10 substance (pyrimidine derivative) under experimentally simulated focal cerebral iscemia in rats. Health Risk Analysis, 2019, no. 1, pp. 103–108. DOI: 10.21668/health.risk/2019.1.11.eng
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Received: 
23.01.2019
Accepted: 
11.03.2019
Published: 
30.03.2019

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