Comparative assessment of various methods of studying the skin toxicity of a wound-healing drug

Abstract

The article presents the results of studying the subacute skin toxicity of a wound-healing cream based on betamethasone dipropionate, gentamicin sulfate, and clotrimazole. According to the Organization for Economic Cooperation and Development (OECD No. 410), the research was conducted using the classic method. When studying the effect of a wound-healing agent on the body of animals during long-term 28-day dermal application by the classical method in animals of the I, II, and III experimental groups, which received the drug in a dose of 0.5, 2.5, and 5 ml/kg body weight; respectively no significant changes were found in the body weight of the animals and the weight coefficients of the liver, heart, spleen, kidneys, and lungs. At the same time, in the animals of the II and III research groups, a slight increase in the concentration of hemoglobin was noted, respectively, by 1.3 and 3.9 %, the level of urea – 5.3 and 11.2 %, the activity of AST – 9.8 and 14.9 % compared to the indicators of animals of the control group. In these groups, there was a decrease in total protein concentration by 5.5 and 6.8 %, creatinine level by 3.1 and 5.3 %, and ALT activity by 6.5 and 9.7 %. The studies conducted according to the OECD No. 410 make it possible to obtain more informative data on the toxic effect of the investigated agent. In particular, it was established that the use of the researched drug in animals of the I, II, and III experimental groups caused a decrease in the weight coefficients of the spleen mass, respectively, by 19.1 (Р < 0.05), 22.4 (Р < 0.05) and 28.3 % (P < 0.05), hearts – 3.6, 4.6 and 7.7 %, kidneys – 4.9, 6.5 and 10.4 % and animal body weight – 4.5, 5.4 and 6.4 %, hemoglobin concentrations – 2.6, 2.9 and 4.4 %, leukocyte counts – 21.4, 16.1 and 15.1 %, hematocrit values – 1.9, 3, 6 and 4.0 %. The average hemoglobin content in the erythrocyte (MSN) also decreased by 8.3, 6.9, and 5.1 %, and the average erythrocyte (MCV) volume was 5.0, 4.7, and 1.7 %. In addition, an increase in weight coefficients of liver mass was established by 10.8 (P < 0.05), 11.8 (P < 0.05), and 15.6 % (P < 0.05). When studying the effect of the researched agent during 28-day dermal application on biochemical indicators of blood serum in animals of the first experimental group, a decrease in the concentration of total protein by 5.8 % was established. Under these conditions, an increase in creatinine level, urea level, ALT, and AST was established, respectively, by 6.2, 18.8 (P < 0.05), 3.8, and 14.7 % (P < 0.05). It should be noted that the use of the researched product in animals of the II and III experimental groups caused an increase in the level of urea, respectively, by 28.6 and 35.7 % (Р < 0.05), creatinine by 8.4 and 3.5 %, AST – 16.4 (P < 0.05) and 11.3 % and the activity of ALT – 8.5 and 11.0 %.