EXPERIMENTAL STUDY OF SUBACUTE TOXICITY OF «DERMABIN»

Abstract

Introduction. One of the most common chronic skin diseases affecting 2 to 3 % of the adult population and 0.5 to 1% of children is psoriasis, chronic recurrent erythematous squamous dermatosis of multifactorial nature. Among medicinal products with various chemical structures, a group of betamethasones is especially worth noticing; that group includes long-acting fluorinated glucocorticosteroids which combined with keratolytics, in particular salycilic acid, have a more pronounced therapeutic effect than each substance individually. Of vital importance for the treatment of dermatoses is a high safety level, tolerability and convenience of the therapy, and one of the most important stages in the development of safe, efficient and competitive medicinal products at the preclinical trial stage is toxicity studies. The purpose of our work was thus to examine subacute toxicity of Dermabin at its 28-day epicutaneous administration.

Investigation methods. Preclinical studies of subacute toxicity of Dermabin were conducted on 40 white outbred rats of both sexes, with masses ranging from 170 to 230 g with daily epicutaneous administration. During 28 observation days, survival, consumption of water and food, body mass and signs of intoxication were recorded based on the overall physical conditions of animals: change of body position, activity, behavior, condition of skin cover, and mucous membranes, body temperature and mass, respiratory rate, and specific symptoms. In all animal groups upon termination of the experiment (day 29), spontaneous daily urine was determined, and full blood count and urinary test were carried out, and after that, to get biological material for calculating mass coefficients of internal organs, animals were withdrawn from the experiment by euthanizing them.

Results and discussion. Findings of other studies show that during the entire observation period, no death of animals was recorded. Condition of skin covers, mucous membranes, consumption of water and food, body temperature, activity and body position in all test groups did not differ from those of control rats. All animals had weight gain without significant differences between groups. Comparison of complete blood count findings at the baseline level and after 28-day administration of Dermabin showed a moderate decrease in WBC count in peripheral blood of test group rats and monocytopenia, lymphocytopenia and eosinopenia. In both test groups, a slight but statistically probable increase in RBC count as compared with control was also found. Hemoglobin content and platelet count remained within the physiological normal range. Blood chemistry showed that a protracted epicutaneous administration of Dermabin to rats did not result in changed activity of aminotransferases and alkaline phosphatase in blood serum, and did not affect the content of creatinine, urea, cholesterol, triglycerides and electrolytes. No significant changes in the clinical urine analysis were observed which could be indicative of an impaired renal function.. Internal organ mass coefficients of test and control animals were within the physiological normal range.

Conclusions. Dermabin in doses of 500 and 1000 mg/kg applied on the skin daily during 28 days does not cause death of animals, has no toxic effect on the overall condition, behavior, consumption of food and water, weight gain, absolute and relative weight of internal organs of rats. A protracted use of Dermabin in the studied doses results in the development of lymphocytopenia, monocytopenia, eosinopenia and slight increase in RBC count and does not change platelet count and hemoglobin content in peripheral blood. Dermabin has no effect on the protein, lipid, carbohydrate metabolism and does not disrupt the function of the hepatobiliary and urinary systems.