DEFINITION OF THE MINIMUM EFFECTIVE DOSE OF WAX MOTH LARVAE TINCTURE IN A MODEL OF TETRACHLOROMETHANE LIVER INJURY IN RATS

Abstract

SUMMARY. In modern medicine, a significant number of various drugs are used to treat various diseases accompanied by increased activity of oxidative processes, which can suppress oxidative stress that occurs in these pathologies and restore protective and compensatory forces in the body. However, despite significant progress in the field of antioxidant pharmacology, the search for new highly effective and low-toxic drugs is constantly ongoing.

The aim – to establish the minimum effective dose of 30 % tincture of wax moth larvae (TWML).

Material and Methods. The studies were conducted on 30 white outbred rats weighing 170-220 g in compliance with all the rules in accordance with the European Convention for the Protection of Vertebrate Animals. To reproduce the model of toxic liver damage in rats, a 50 % oil solution of carbon tetrachloride was used at a dose of 1 ml/kg of animal body weight twice (every other day). The animals were euthanized under thiopental anesthesia 4 days after the last administration of carbon tetrachloride (toxicogenic phase). 30 % wax moth tincture was used at doses of 20, 25, 30, 40 mg/kg. The effectiveness of the tincture was assessed by the following indicators: the content of TBA-active products, catalase activity, ceruloplasmin (CP) content and aminotransferase (ALT and AST) activity. Statistical analysis and processing of the obtained data was carried out using Microsoft Office Excel 2016 software (Microsoft Corp., USA). Changes were considered significant at p≤0.05.

Results. We noted a 1.6-fold increase in the content of TBA-AP in the blood serum relative to the level of intact rats on the 4th day from the last administration of carbon tetrachloride. Doses of 0.25 ml/kg; 0.3 ml/kg and 0.4 ml/kg showed an effective effect on the index of the lipoperoxidation process, which led to a significant decrease (p≤0.05) in the content of TBA-AP in the blood serum of intoxicated rats. After the administration of CCl₄, inhibition of the activity of the antioxidant defense system was observed, as evidenced by a significant decrease in catalase activity (p≤0.05) in the blood serum. The dose of 0.2 ml/kg of TWML used by us did not lead to a significant increase in this indicator, all subsequent doses of the studied tincture were effective. On the 4th day of development of toxic hepatitis, doses of 0.25 ml/kg showed an effective effect on the content of CP; 0.3 ml/kg and 0.4 ml/kg body weight of rats, after which the content of this protein decreased, approaching the normal level.

In rats intoxicated with carbon tetrachloride, on the fourth day, the activity of ALT in the blood serum increased by 54 %, AST – by 38 %. Administration of the tincture to the poisoned animals at a dose of 0.25 ml/kg of body weight and higher doses caused a significant decrease (p≤0.05) in the activities of aminotransferases.

After the rats were affected by carbon tetrachloride, a significant increase in the content of TBA-AP in the liver, a decrease in catalase activity and aminotransferases was noted. The tincture we used at doses of 0.2 ml/kg and 0.25 ml/kg was ineffective in relation to the content of TBA-AP and the activity of ALT and AST in the liver of the affected rats. Catalase activity significantly (p≤0.05) increased in this organ after the use of a dose of 0.25 ml/kg of animal body weight.

Conclusions. The conducted studies showed that the minimum effective dose under the conditions of carbon tetrachloride-induced hepatitis is a dose of tincture of wax moth larvae of 0.25 ml/kg body weight of rats. At this dose, it exhibits pronounced antioxidant, membrane-protective and hepatoprotective properties.