EFFECT OF COURSE ADMINISTRATION OF 11-DEOXYMISOPROSTOL ON FREE RADICAL OXIDATION IN THE BRAIN

For a systemic analysis of the anti- or pro-oxidant properties of 11-deoxymisorostole (11-DMP) in vivo, the test compound was administered intragastrically in 3 doses daily, followed by assessment of the levels of lipid peroxidation products and oxidative modification of proteins in the brain. In the course of experimental studies, it was established that activation of catalase was observed in brain cell homogenates at certain periods of administration of 11-DMP at doses of 1.0 and 2.0 mg/kg; a moderate increase in metal-catalyzed oxidative modification of proteins (OMP) on the 3rd and 7th days of administration of 11-DMP at doses of 1.0 and 2.0 mg/kg; increase in the capacity of lipophilic antioxidant defense, depending on the dose of 11-DMP. The studies performed showed that the administration of 11-DMP in courses over 3 and 7 days is characterized by a redistribution of free radical oxidation (FRO) processes in the brain without pro-oxidant effects. Research results show the most pronounced antioxidant activity of the test compound when administered in a course of doses of 1.0 and 2.0 mg/kg.

Objective: to determine the anti- or pro-oxidant properties of 11-DMP in the brain during its course administration at doses of 0.5, 1.0 and 2.0 mg/kg.

Material and methods. The test substance (ethyl ester (±)-11,15-dideoxy-16-methyl-16-hydroxyprostaglandin E1, 11-DMP) was synthesized and provided for research by the laboratory for the synthesis of low molecular weight bioregulators of the Ufa Institute of Chemistry, Russian Academy of Sciences, Ufa. Experimental studies were carried out on 120 white laboratory rats. In brain homogenates of experimental animals, the levels of primary, secondary, and end products of lipid peroxidation, oxidative modification (carbonylation) of proteins (OMP), and activity of key antioxidant defense enzymes were determined.

Results and discussion. It was found that the introduction of 11-DMP was not accompanied by the accumulation of free radical oxidation products in the brain. The results of the studies show that the course administration of 11-DMP for three and seven days is accompanied by a redistribution of free radical oxidation processes in the brain without a prooxidant effect: the power of lipophilic antioxidant defense (AOD) systems increases while the reserve-adaptive potential of proteins is limited.

Conclusion. The results obtained allow us to draw conclusions about the presence of both direct and indirect antioxidant activity in the studied compound, which is most pronounced with a course (3-time, 7-time) daily intragastric administration at doses of 1.0 and 2.0 mg/kg.

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