Comparative Evaluation of Hepatoprotective Activity of Xymedon Preparation Derivatives with Ascorbic Acid and Methionine

© 2017, Springer Science+Business Media, LLC. The main objective of this work was a comparative evaluation of hepatoprotective activity of pyrimidine derivative of the active compound of Xymedon (1-(ß-oxyethyl)-4.6-dimethyl-1.2-dihydro-2-oxopirimidon) and its derivatives with methionine and ascorbic acid. The experiment was conducted on nonlinear white rats of both sexes based on the model of toxic damage inflicted on liver by CCl 4 with prophylactic scheme. The compounds were injected at doses of 1/500 LD 50 (13 mg/kg for Xymedon and 11 mg/kg for its derivatives with ascorbic acid and methionine). The study showed that, out of the three compounds considered, the Xymedon derivative with ascorbic acid had the most prominent hepatoprotective properties, as, given the CCl 4 poisoning, it caused the greatest decrease of liver damage area (by a factor of 3.25 over control) and change of the largest number of biochemical markers towards normalization. The Xymedon derivative with methionine had less prominent hepatoprotective properties than both the derivative with ascorbic acid and Xymedon itself

Neuroprotective action of new pyrimidine derivatives on rat spinal cord injury

Effects of the systemic administration of xymedon and its derivatives-L-ascorbate and para-aminobenzoate 1,2-dihydro-4,6-dimethyl-l-(2-hydroxyethyl) pyrimid-2-one (compounds 29D and 34D, respectively) - have been studied on a contusion model (Th8 level) of spinal cord injury in rats. Experiments showed the impact of treatment on recovery of motor function, spinal cord tissue safety, population and phenotypic characteristics of astrocytes in the zones of gray and white matter. Xymedon produced a stimulating effect on recovery of the locomotor function. In this respect, compounds 29D and 34D were more effective than xymedon, although no significant differences between the action of compounds 29D and 34D was observed. Each of the three investigated pyrimidine derivatives significantly reduced the total area of pathologic cavities in spinal cord. In this respect, compounds 29D and 34D were also more effective than xymedon. Compound 29D exhibited a more pronounced effect in the dorsal root entry zone (DREZ), while compound 34D more significantly supported preservation of tissue in the ventral horns (VHs). Within 60 days after administration of compounds of 29D and 34D, the number of GFAP+ astrocytes in gray matter zones decreased as compared to the group treated with xymedon, and the expression of this marker protein of intermediate filaments decreased. In the white matter, the number of GFAP+ cells increased under the influence of compound 29D and decreased under the action of compound 34D. Differences between the effects of compounds 29D and 34D (on the background of their equal influence on recovery of the locomotor function) may be indicative of different cellular and molecular mechanisms of action, in agreement with data on their action on tissue safety

Evaluation of the Hepatoprotective Effect of L-Ascorbate 1-(2-Hydroxyethyl)-4,6-Dimethyl-1,2-Dihydropyrimidine-2-One Upon Exposure to Carbon Tetrachloride

© 2017, Springer Science+Business Media New York.Hepatoprotective properties of a new pyrimidine derivative — L-ascorbate 1-(2-hydroxyethyl)-4,6-dimethyl-1,2-dihydropyrimidine-2-one, synthesized on the basis Xymedon, were assessed in white rats exposed to CCl4. The compound under study administered prior to exposure to CCl4 reduced the deviation of biochemical parameters from reference values and severity of structural and morphological changes in liver, when compared to the control. Hepatoprotective properties of the studied compound were more pronounced than those of Xymedon

Pyrimidine Derivative Ameliorates Spinal Cord Injury via Anti-apoptotic, Anti-inflammatory, and Antioxidant Effects and by Regulating Rho GTPases

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. One of the most important strategies for the treatment of spinal cord injury is searching for new and effective pharmacological neuroprotectors and regeneration stimulators. The derivatives of pyrimidine are universal stimulators of the regeneration of various tissues as they support the recovery of nervous structures. The protective effect of the cocrystal of 1,2-dihydro-4,6-dimethyl-1-(2-hydroxyethyl)-pyrimidinone-2 with para-aminobenzoic acid (compound conjugate III, CCIII) was explored on a rat model with a contusion spinal cord injury. Injection of CCIII significantly reduced the expression of tumor necrosis factor α (TNF-α), inhibited the synthesis of myeloperoxidase (MPO), matrix metalloproteinase 9 (MPP9), cyclooxygenase-2 (COX2), and macrophage marker CD68, and increased the level of superoxide dismutase 1 (SOD1). Additionally, the expression of caspase-7 markers in the damaged tissue decreased under the action of CCIII. Treatment with the CCIII maintained a population of Olig2-positive myelin-forming cells at 30 days post-injury. The detected therapeutic effect is comparable with that of riluzole

Efficiency of new pyrimidine derivativs influence on physical working capacity of rats in the test 'swimming to failure'

© Northern State Medical University. There have been studied effects of xymedon and six new pyrimidine derivatives, that are close and distant analogs of xymedon, on rats' working capacity in the test "swimming to failure". It has been shown that a single administration of the studied compounds did not have a statistically significant effect in the test. In the conditions of multiple intraperitoneal administration of the studied pyrimidine derivatives, the compound L-ascorbate, 1-(2-hydroxyethyl)-4.6-dimethyl-1.2-dihydropyrimidine-2-one had the lowest toxicity and the most pronounced actoprotective effect. Introduction in the dose of 20 mg/kg caused a statistically significant increase 440 % in the duration of swimming of rats on the 14th day of the experiment compared with the control group. Multiple administration of the compound in the conditions of physical load did not affect leucopoiesis, but stimulates erythropoiesis resulting in an increase in the number of erythrocytes and a hemoglobin level. The substance introduction under mixed exhausting loads prevented such changes of blood biochemical parameters as reduction of glucose, increased of urea and lactic acid levels, what indicates improvement in the animals' tolerability of loads and an anti-catabolic effect of the compound. Absence of hepato- and cardiotoxic effects of the substance has been shown

Efficiency of new pyrimidine derivativs influence on physical working capacity of rats in the test 'swimming to failure'

© Northern State Medical University. There have been studied effects of xymedon and six new pyrimidine derivatives, that are close and distant analogs of xymedon, on rats' working capacity in the test "swimming to failure". It has been shown that a single administration of the studied compounds did not have a statistically significant effect in the test. In the conditions of multiple intraperitoneal administration of the studied pyrimidine derivatives, the compound L-ascorbate, 1-(2-hydroxyethyl)-4.6-dimethyl-1.2-dihydropyrimidine-2-one had the lowest toxicity and the most pronounced actoprotective effect. Introduction in the dose of 20 mg/kg caused a statistically significant increase 440 % in the duration of swimming of rats on the 14th day of the experiment compared with the control group. Multiple administration of the compound in the conditions of physical load did not affect leucopoiesis, but stimulates erythropoiesis resulting in an increase in the number of erythrocytes and a hemoglobin level. The substance introduction under mixed exhausting loads prevented such changes of blood biochemical parameters as reduction of glucose, increased of urea and lactic acid levels, what indicates improvement in the animals' tolerability of loads and an anti-catabolic effect of the compound. Absence of hepato- and cardiotoxic effects of the substance has been shown

Pyrimidine Derivative Ameliorates Spinal Cord Injury via Anti-apoptotic, Anti-inflammatory, and Antioxidant Effects and by Regulating Rho GTPases

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. One of the most important strategies for the treatment of spinal cord injury is searching for new and effective pharmacological neuroprotectors and regeneration stimulators. The derivatives of pyrimidine are universal stimulators of the regeneration of various tissues as they support the recovery of nervous structures. The protective effect of the cocrystal of 1,2-dihydro-4,6-dimethyl-1-(2-hydroxyethyl)-pyrimidinone-2 with para-aminobenzoic acid (compound conjugate III, CCIII) was explored on a rat model with a contusion spinal cord injury. Injection of CCIII significantly reduced the expression of tumor necrosis factor α (TNF-α), inhibited the synthesis of myeloperoxidase (MPO), matrix metalloproteinase 9 (MPP9), cyclooxygenase-2 (COX2), and macrophage marker CD68, and increased the level of superoxide dismutase 1 (SOD1). Additionally, the expression of caspase-7 markers in the damaged tissue decreased under the action of CCIII. Treatment with the CCIII maintained a population of Olig2-positive myelin-forming cells at 30 days post-injury. The detected therapeutic effect is comparable with that of riluzole

Efficiency of new pyrimidine derivativs influence on physical working capacity of rats in the test 'swimming to failure'

© Northern State Medical University. There have been studied effects of xymedon and six new pyrimidine derivatives, that are close and distant analogs of xymedon, on rats' working capacity in the test "swimming to failure". It has been shown that a single administration of the studied compounds did not have a statistically significant effect in the test. In the conditions of multiple intraperitoneal administration of the studied pyrimidine derivatives, the compound L-ascorbate, 1-(2-hydroxyethyl)-4.6-dimethyl-1.2-dihydropyrimidine-2-one had the lowest toxicity and the most pronounced actoprotective effect. Introduction in the dose of 20 mg/kg caused a statistically significant increase 440 % in the duration of swimming of rats on the 14th day of the experiment compared with the control group. Multiple administration of the compound in the conditions of physical load did not affect leucopoiesis, but stimulates erythropoiesis resulting in an increase in the number of erythrocytes and a hemoglobin level. The substance introduction under mixed exhausting loads prevented such changes of blood biochemical parameters as reduction of glucose, increased of urea and lactic acid levels, what indicates improvement in the animals' tolerability of loads and an anti-catabolic effect of the compound. Absence of hepato- and cardiotoxic effects of the substance has been shown

Comparative Evaluation of Hepatoprotective Activity of Xymedon Preparation Derivatives with Ascorbic Acid and Methionine

© 2017, Springer Science+Business Media, LLC. The main objective of this work was a comparative evaluation of hepatoprotective activity of pyrimidine derivative of the active compound of Xymedon (1-(ß-oxyethyl)-4.6-dimethyl-1.2-dihydro-2-oxopirimidon) and its derivatives with methionine and ascorbic acid. The experiment was conducted on nonlinear white rats of both sexes based on the model of toxic damage inflicted on liver by CCl 4 with prophylactic scheme. The compounds were injected at doses of 1/500 LD 50 (13 mg/kg for Xymedon and 11 mg/kg for its derivatives with ascorbic acid and methionine). The study showed that, out of the three compounds considered, the Xymedon derivative with ascorbic acid had the most prominent hepatoprotective properties, as, given the CCl 4 poisoning, it caused the greatest decrease of liver damage area (by a factor of 3.25 over control) and change of the largest number of biochemical markers towards normalization. The Xymedon derivative with methionine had less prominent hepatoprotective properties than both the derivative with ascorbic acid and Xymedon itself

Neuroprotective action of new pyrimidine derivatives on rat spinal cord injury

Effects of the systemic administration of xymedon and its derivatives-L-ascorbate and para-aminobenzoate 1,2-dihydro-4,6-dimethyl-l-(2-hydroxyethyl) pyrimid-2-one (compounds 29D and 34D, respectively) - have been studied on a contusion model (Th8 level) of spinal cord injury in rats. Experiments showed the impact of treatment on recovery of motor function, spinal cord tissue safety, population and phenotypic characteristics of astrocytes in the zones of gray and white matter. Xymedon produced a stimulating effect on recovery of the locomotor function. In this respect, compounds 29D and 34D were more effective than xymedon, although no significant differences between the action of compounds 29D and 34D was observed. Each of the three investigated pyrimidine derivatives significantly reduced the total area of pathologic cavities in spinal cord. In this respect, compounds 29D and 34D were also more effective than xymedon. Compound 29D exhibited a more pronounced effect in the dorsal root entry zone (DREZ), while compound 34D more significantly supported preservation of tissue in the ventral horns (VHs). Within 60 days after administration of compounds of 29D and 34D, the number of GFAP+ astrocytes in gray matter zones decreased as compared to the group treated with xymedon, and the expression of this marker protein of intermediate filaments decreased. In the white matter, the number of GFAP+ cells increased under the influence of compound 29D and decreased under the action of compound 34D. Differences between the effects of compounds 29D and 34D (on the background of their equal influence on recovery of the locomotor function) may be indicative of different cellular and molecular mechanisms of action, in agreement with data on their action on tissue safety