Pre-clinical evaluation of metabolic and morphological changes in the body induced by 4-chlorobenzhydryl pip

Abstract

Introduction. A significant medical and social challenge in occupational health poses a risk of chemical intoxication in the industrial synthesis of new drug compounds.The aim of the work was a pre-clinical study of metabolic and morphological changes in acute and subchronic exposure of 4-chlorobenzhydryl piperazine on the body, which will allow early diagnosis of health problems in workers in workshops where the reaction synthesis of piperazine compounds are used and carried out.Material and methods. A complex of toxic-hygienic and biochemical studies was carried out. The object of the research was 4-chlorobenzhydryl piperazine. Toxic properties were studied in experiments on white outbred rats. Single inhalation and subacute intragastric modes and methods of exposure were reproduced. Blood serum indices were analyzed: the activity of aspartate aminotransferase, alanine aminotransferase, catalase, the concentration of total protein, ceruloplasmin, urea, cholesterol, and glucose. The content of protein and chlorine ions was determined in the urine. Morphological studies were performed on the brain, heart, lungs, liver, kidneys, spleen, stomach, pancreas, and thyroid glands.Results. The changes in the biochemical indices of blood and urine in different ways of substance intake into the body were similar. An increase in the concentration of ceruloplasmin, which has a pronounced oxidase activity, was revealed. A decrease in catalase activity demonstrated the lack of antioxidant protection in the conditions of intoxication. A marker of dysfunctional liver disorders was an increase in the activity of aminotransferases. In rats, in the priming process, no changes in indices characterizing the functional state of the kidneys were revealed. 4-chlorobenzhydryl piperazine has the most pronounced toxic effect on the hepatobiliary system. Histological findings confirmed the development of mild toxic steatohepatosis in animals exposed to poisoning.Conclusion. When 4-chlorobenzhydryl piperazine is ingested, there is a risk of pathology, especially of the hepatobiliary system. The information content of biochemical indices that can become correct signs of health disorders in workers who are in contact with 4-chlorobenzhydryl piperazine is considered. The indices possessing not only high sensitivity but the activity of aminotransferases, the concentration of urea, and ceruloplasmin in blood serum also can provide diagnostically significant specificity.