Research on acute and chronic toxity of the experimental drug Аmprolinsyl

Abstract

The drug Amprolinsyl is a is a mixture of hydrochloric amprolium (12.5 g) and milled fruits of the milk thistle (up to 100 g), designed to prevent and treat protozoonoses in birds, especially when mixed associative invasions occur. The fruits of the milk thistle contain the natural vitamins (A, C, E, B) and the minerals (copper, iron, cobalt) and other factors that significantly expand and enhance the pharmacological effect of the drug Amprolinsyl. We found that when the drug Amprolinsyl was administered intra gastrically to white rats at a dose of 5000 mg/kg and higher clinical signs of toxicity occurred after 4–5 hours. Damage to motor activity and tremors of individual muscles of these animals was observed. The rats died after 1–4 days. A direct relationship was found between the drug at a specific dosage and the death of rats. After intra gastric administration of the drug Amprolinsyl to white rats clinical signs of toxicity appeared after 5–6 hours at a dose of 4000 mg/kg body weight. These animals attempted to gather in groups and to hide in the bedding. The death of the mice occured in 1–3 days. Thus, LD50 drug of Amprolinsyl following intra gastric administration to white rats was 5,917 and for white mice 5,167 mg/kg. After studying the cumulative properties of Amprolinsyl, it was found that the total drug administered in average doses was 831 mg/kg, and the cumulative rate – 8.31. Long-term daily intragastric administration of Amprolinsyl over 24 days affected the functional state of the liver and kidneys. The magnitude of weight ratios of lungs, heart and spleen during the research period was the same as in the control group of rats. Significant changes were found only after analyzing the leukocyte profile. A reduction was observed in the number of neutrophils to 54.7% and an increase in the number of lymphocytes to 9.2%. Following prolonged daily administration of increasing doses Amprolinsyl causes a slight degradation of the membranes of hepatocytes, which indicates increased activity of aminotransferases.When investigating the chronic toxicity of Amprolinsyl it was found that at doses of 1/50 LD50, and 1/100 LD50 the drug had no effect on the results of functional tests, due to the normal functioning of the liver tissue and the lack of negative impact on animals in the 3rd and 4th groups. Administration of the the drug at doses of 1/20, 1/50 and 1/100 LD50 over 30 days did not significantly affect the functional state of the internal organs of the experimental animals. When investigating the morphological blood parameters of the rats following oral administration of Amprolinsyl at different doses a downward trend in the haemoglobin and colour index value and a likely reduction in the number of white blood cells, compared to the control group was observed in all experimental groups. According to the values of haematological and biochemical parameters, it was established that in spite of the low toxicityof Amprolinsyl at doses of 1/20 and 1/50 LD50 the drug had an effect on lipid metabolism, as was shown following the increase of glycerol.