Study of acute and chronic toxicity of feed additive based on vermiculture

The paper presents the results of study of the toxicity of a feed additive, which includes Leuzea safflower (Rhaponticum carthamoides) and protein obtained from vermiculture. The acute toxicity of the feed additive was studied in 31 SD white rats. It has been established that the acute oral toxicity of the feed additive is above 2500 mg/kg, which makes it possible to classify the feed additive as hazard class 3 and classify it as “moderately hazardous” according to GOST 12.1.007-76. The chronic toxicity of the feed additive was studied in 22 SD white rats. The feed additive was administered orally at a dose of 120 and 1200 mg/kg for 30 days. Long-term effects were assessed 14 days after the last introduction of the feed additive. To assess the toxic effects, the effect of the additive on the general condition of the animals, food and water intake was evaluated, blood and urine were analyzed. Complete blood count was carried out by standard methods with the determination of the following parameters: hematocrit, hemoglobin level, the number of erythrocytes, platelets, leukocytes, eosinophils, segmented neutrophils, lymphocytes and monocytes. The study of biochemical parameters of blood was carried out using standard kits for biochemical analysis. The following indicators were determined: ALT, total bilirubin, glucose, creatinine and urea. The urinalysis included the determination of the following indicators: density, leukocytes, nitrites, pH, erythrocytes, protein,  glucose, ascorbic acid, ketones, urobilinogen, bilirubin. There was no statistically significant difference in blood and urine parameters between the animals of the control and experimental groups. A pathohistological examination of the stomach, liver, kidneys and heart was carried out, which showed the absence of a toxic effect of the feed additive. Local irritant action was studied in pathomorphological studies. It has been established that the feed additive does not have an irritating effect at the injection site. Thus, the feed additive can be used in feeding farm animals and birds at the recommended dose

Powerful Potential of Polyfluoroalkyl-Containing 4-Arylhydrazinylidenepyrazol-3-ones for Pharmaceuticals

4-Arylhydrazinylidene-5-(polyfluoroalkyl)pyrazol-3-ones (4-AHPs) were found to be obtained by the regiospecific cyclization of 2-arylhydrazinylidene-3-(polyfluoroalkyl)-3-oxoesters with hydrazines, by the azo coupling of 4-nonsubstituted pyrazol-5-oles with aryldiazonium chlorides or by the firstly discovered acid-promoted self-condensation of 2-arylhydrazinylidene-3-oxoesters. All the 4-AHPs had an acceptable ADME profile. Varying the substituents in 4-AHPs promoted the switching or combining of their biological activity. The polyfluoroalkyl residue in 4-AHPs led to the appearance of an anticarboxylesterase action in the micromolar range. An NH-fragment and/or methyl group instead of the polyfluoroalkyl one in the 4-AHPs promoted antioxidant properties in the ABTS, FRAP and ORAC tests, as well as anti-cancer activity against HeLa that was at the Doxorubicin level coupled with lower cytotoxicity against normal human fibroblasts. Some Ph-N-substituted 4-AHPs could inhibit the growth of N. gonorrhoeae bacteria at MIC 0.9 μg/mL. The possibility of using 4-AHPs for cell visualization was shown. Most of the 4-AHPs exhibited a pronounced analgesic effect in a hot plate test in vivo at and above the diclofenac and metamizole levels except for the ones with two chlorine atoms in the aryl group. The methylsulfonyl residue was proved to raise the anti-inflammatory effect also. A mechanism of the antinociceptive action of the 4-AHPs through blocking the TRPV1 receptor was proposed and confirmed using in vitro experiment and molecular docking