Keywords
Abstract
Intoxications of different etiology, requiring symptomatic emergency therapy, is one of the most common pathological conditions in clinical practice. Toxins, penetrating into cells through defects in biological membranes, cause a violation of intracellular metabolism, cytolysis, which leads to the appearance of autoantigens, a violation of the distribution and dissemination of cytolocalized substances, the formation of pathological metabolites and their hyperconcentration. Therefore, the search for new detoxifiers today is quite an urgent problem. Accelerating and reducing the cost of new detoxifying agents in medical institutions directly depends on the proper conduct of their specific activity in preclinical studies through the use of new experimental approaches and optimized models. The aim of the study was to optimize an approach to evaluation of oral detoxifiers effectiveness under the model of acute ethanol intoxication on rats. The study was carried out on white male rats weighing 180–200 g. 20 animals were selected for the experiments. They were divided into 2 groups of 10 animals each. To simulate acute intoxication, the animals of the experimental group were orally administered 40% solution of ethyl alcohol at a dose of 8.0 g/ kg of body weight (1 LD50) in two doses with an interval of 15 minutes. Animals of the second group, which served as intact control, received water for injection at a dose of 5.0 ml/kg in the same mode as the experimental animals. Given the strong toxic response during the experiment, animals from experimental group, which fell into a deep coma within 30 minutes after ethanol administration, were taken out of the experiment, due to the impossibility of further use of the detoxification drugs planned for testing to such rats because of the risk of aspiration in respiratory tract. Such animals were replaced by others given similar numbers. The observation period for experimental animals was 4 days. The death of the animals was recorded immediately after it was established. Life expectancy, neurological status, indicators of emotional and motor activity were assessed. Serum biochemical indicators were also determined to compare the sensitivity of all determined parameters for monitoring the acute intoxication model. It was confirmed to be highly informative an evaluation of animal's neurological status and motor activ ity in «Open field» test, but not serum biochemical indicators when reproducing the model of acute ethanol intoxication. It was also shown that up to 30 % of experimental animals can be weeded out due to comatose state and this should be taken into account when experiment planning. An optimized approach proposed to evaluation of oral detoxifyers under the model of acute alcohol intoxication in laboratory animals allows to study various degrees of manifestation of this pathology due to their temporary monitoring, which is of great importance for screening studies of such drugs.