Humic acids are characterized by chelating properties due to which they are able to influence the mineral metabolism in animals. Rabbits have species-specific characteristics of mineral metabolism, which distinguishes them from most species of mammals. For the experiment, 16 rabbits of 45-day-old of Hyplus breed were divided into the experimental and control group of 8 rabbits in each. The animals were 15 days in the preparatory period. The rabbits of the experimental group received humic acid additive individually with water in the amount of 5 mg/kg, the rabbits of the control group received pure water in the same amount. The ability of humic acid additive to increase the content of calcium, ionized calcium, iron, to correct the content of copper and zinc, and also to increase the activity of alkaline phosphatase in the blood serum of rabbits of the experimental group has been proved. We observed the early effect of the humic acid additive on increasing the content of iron and calcium ionized and a later effect on the activity of alkaline phosphatase and an increase in the content of copper in the blood serum. The influence of humic acid additive on the distribution of calcium, phosphorus, manganese, copper and zinc in bone tissue is determined. According to a histological study, there was a significant increase in the number of layers of osteons and osteoblasts in the bone tissue of the femur, an increase in the number of osteons and osteoblasts in the bone tissue of the sternum and an increase in the number of columns of chondrocytes and an increase in the number of chondrocytes in the column in the cartilaginous tissue of the sternum. The results of a histological study of bone tissue, together with an increase in structural macroelements in it and redistribution of osteotropic trace elements in the blood and bone tissue suggest the possibility of using a humic acid additive to intensify the growth and mineralization of bone tissue, which can improve the state of bone tissue of rabbits in the postnatal period ontogenesis.
The article deals with the method of preparation of the liniment, the type of oil solution, based on thio-derivative of triazole. In order to determine the degree of the solution of the investigating substance in the Saint-Marry-thistle (silybum marianum) oil, other physical properties (capacity to stratification, hydrophilicity) and antimicrobial, antifungal action, the medical forms of the concentration at 1, 3, 5, 7, 10, 12, 15% were made. For the preparation of non-lethal oil solution,it was used the classical technology with the loading of the solvent in the order of increasing viscosity or density. The active substance weighed on the analytical scales (PCR-246) was put in dry bottles and was filled with the calculated mass of the thistle oil. To provide faster dissolution of the chemical compound in the oil, the vial was heated in a water bath (40–50 °C). It has been established that the new-synthesized compound is well soluble in thistle oil in the forms at 1, 3, 5 and 7%. The obtained solutions were marked by transparency, lack of sediment in the haze. The critical limit of solubility was 10% solution. For moderate solubility and light clouding, such crystallization was typical for such solutions, which disappeared in 10–15 minutes on the condition of heating it in a water bath 18–20 °C). At higher concentrations (12 and 15%) the investigated chemical compound was littlesoluble and insoluble, precipitated (felt out in sediment) and crystallized. The concentration of the solution (1, 3, 5 and 7%) was characterized by resistance to bundle. For 10% solutions of the investigating dosage form, there was a slight stratification with signs of crystallization on the verge. Sorbent capacity of oil solutions is insignificant and stops after 2 hours. According to the assessment of the effect of the new- developed therapeutic agent on microorganisms and fungi, a deleterious effect on S. aureus and C. albicans and A. niger was noted, which provides the basis for preclinical studies on laboratory animals, especially with the patterns of solution at 7 and 10% concentration.
The toxicity parameters of "VetMikoDerm" for one-time and long-term skin treatment were investigated. The studied liniment as an off-white substance has a thio derivative of 1,2,4-triasole. Spotted thistle oil is used as a solvent. The research of the determination of acute and low acute skin toxicity has been performed on young, healthy, healthy skin of the laboratory rats. The drug was applied in different doses to the stripped areas of the skin (area is not less than 10% of the total area of the skin). It was established that after a single application of the drug (24 hours) in a dose of less than 2000 mg/kg of body weight, the death of experimental animals or any signs of general intoxication of the body is not observed. Local reaction (redness, itching, allergy, combing) is absent. According to GHS under the assessment in this dose studying the "VetMicoDerm" drug belongs to the 5th safety category (Grade 5, not classified). During a long-lasting application of the drug (28 days), the death of the rats was not adversed, the animals had a preserved appetite, responded adequately to external stimuli, reflex excitability was completely preserved. Under hematological and biochemical studies of blood of the experimental animals, it was found that against the backdrop of insignificant increase in the number of white blood cells in their blood, the number of neutrophils increases and the percentage of lymphocytes decreases significantly. However, under the usage of the drug in the therapeutic dose (50 mg/kg body weight) the liver function has a tendency to increase. Increasing in dose (500 mg/kg) of the VetMikoDerm a 10-fold continued its application which led to an increase in serum concentrations of urea and creatinine,increasing the mass index can serve as a marker of renal decline functional condition of the body.Key words: acute and subacute toxicity, rats, "VetMikoDerm", hematological and biochemical parameters of blood.
The investigation of the skin toxicity of the liniment "VetMikoDerm" for prolonged use was performed on young and healthy laboratory rats with intact skin, body weight 200-220 g. The investigated environment was applied to a clean, non-woolly area (dorsal/lateral surface) of at least 10% of the total surface area. The spotted thistle oil was applied to the pre-prepared area of the skin of the animals of the control group, and the other two experimental groups of animals got the studied drug at the doses of 50 (I) and 500 mg/kg (II), respectively. The drug was applied to the skin daily for 28 days. At the end of the experiment, after the decapitation of the rats conducted under the light etheric anesthesia, a complete pathoanatomical dissection was performed, the coefficients of the mass of the internal organs were determined, samples of liver, kidney and skin tissues were taken for their histological examination. According to the results it was established that the liver and kidneys histology, and skin of rats of the 1st experimental group were similar to those that were of the control animals. At the same time, receiving the maximum dose (10 times the therapeutic dose) of the drug "VetMikoDerm", the majority of rats of the 2nd group showed a discomplication of the lamellar structure of the liver lobules, hepatocytes were placed in separate groups, sinusoidal capillaries were expanded. The presence of hepatocytes with heterogeneous, granular and weakly colored cytoplasm was observed in the central parts of the lobules, the nuclei of individual hepatocytes were increased, indicating the development of granular protein degeneration of the parenchyma. Histologically, under these conditions, foci of granular dystrophy of the epithelium of the vorticular and direct renal tubules with the expansion of their lumen were found in the structure of kidney of rats. The kernels of individual nephropyelitis had signs of karyopicnosis and cariorexis. The histological structure of skin of rats in all experimental groups was of the same type and consisted of the epidermis, dermis and hypodermis. Animals of the 2nd experimental group which repeatedly and for a long time were applied a "VetMikoDerm" lineulation in a dose that exceeded its optimal amount by 10 times showed the epidermal thickening, the presence of smallmesenchymal polymorphocytic infiltration, microcirculatory corneal disorder and sebaceous gland hyperplasia glands in the dermis that indicated the development of a compensatory-adaptive reaction in places of application of a 10-fold dose of the investigational medicinal product. Гістоструктура внутрішніх органів та шкіри щурів за довготривалої дії препарату "ВетМікоДерм"В.П. Мартинишин Львівський національний університет ветеринарної медицини та біотехнологій імені С.З. Ґжицького, м. Львів, Україна Вивчення нашкірної токсичності лініменту "ВетМікоДерм" за тривалого застосування проводили на молодих і здорових лабораторних щурах з непошкодженою шкірою, масою тіла 200-220 г. Досліджуваний засіб наносили на чисту бе...
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