ОСОБЛИВОСТІ ПОКАЗНИКІВ ВІЛЬНОРАДИКАЛЬНОГО ОКИСНЕННЯ І АНТИОКСИДАНТНОЇ СИСТЕМИ У ТВАРИН ЗА УМОВ ГОСТРОГО ТОКСИЧНОГО ТА СУБХРОНІЧНОГО УРАЖЕННЯ АЦЕТАМІНОФЕНОМ НА ТЛІ ДОВГОТРИВАЛОГО ЗАСТОСУВАННЯ ЕСТРОГЕНІВ ТА ПРОГЕСТИНІВ ПРИ КОРЕКЦІЇ ТІОТРИАЗОЛІНОМ ТА ГЕПАДИФ

Abstract

FEATURES OF FREE RADICAL OXIDATION AND ANTIOXIDANT SYSTEM PARAMETRS OF ANIMALS AT ACUTE TOXIC AND SUBCHRONIC POISONING BY ACETAMINOPHEN WITH PROLONGED USAGE OF ESTROGEN AND PROGESTIN AT THE CORRECTION BY THIOTRIAZOLINE AND HEPADIF

I.B. Ivanusa

TernopilStateMedicalUniversity

Activation of lipid peroxidation of animals at poisoning by acetaminophen with prolonged usage of estrogen and progestin are investigated. This is evidenced by increased concentration of reactive oxygen species by mononuclear leukocytes, the content of lipid peroxidation products: malondialdehyde, diene and triene conjugates. The ability of the corrective factors inhibits the formation of these products in the plasma and homogenate can indirectly evidenced about the antioxidant properties of the drug. So it is interested to investigate the influence of thiotriazoline and hepadif on activity of these processes in rats, which are poisoned by acetaminophen with prolonged usage of estrogen and progestin.

KEY WORDS: acetaminophen, thiotriazoline, hepadif, free radical oxidation of lipids and proteins, antioxidant system.

INTRODUCTION. Acetaminophen is present in more than 200 drugs at various brand names. Almost all of them are used as analgesic and antipyretics. Poisoning may be at usages a big single dose of pure drug or combined drugs containing acetaminophen. Hepatoprotectors are one of the most widely using drugs for the treatment of liver diseases. These drugs are used for metabolism normalization, increase resistance to pathogenic factors, normalization of functional activity and stimulation of reparative - regenerative processes in the liver.

Therefore, we set a goal to investigate the effect of acetaminophen on parameters of free radical oxidation and antioxidant system of animals at poisoning by acetaminophen with prolonged usage of estrogen and progestin at the correction by Thiotriazoline and Hepadif.

INVESTIGATION METHODS. The experiments were performed on white female rats weighing 200 ±20 g, are kept on a standard diet of vivarium and free access to water.

We did three series of experiments. In the first experiment: toxic damage of rats caused by a single intragastric administration of acetaminophen suspension in 2% starch solution at a dose of 1250 mg/kg body weight (1/2 LD₅₀), the second - a suspension of acetaminophen in 2% starch solution at a dose of 55 mg/kg (highest therapeutic dose) is administered within 7 days. Levonorgestrel in 2% solution of starch is administered both series intragastric at a dose of 1.17 mg/kg, and ethinylestradiol - a dose of 0.23 mg/kg within 40 days. Thiotriazoline was injected intraperitoneally at a dose of 100 mg/kg; Hepadyf - intraperitoneally at a dose of 8.6 mg/kg.

In 1 series of experiments, the experimental rats were divided into 3 groups: 1st - intact (control); 2nd – poisoning by acetaminophen after 40-day administration of levonorgestrel and ethinylestradiol, 3rd - poisoning by acetaminophen after 40-days administration of levonorgestrel, ethinylestradiol and once Thiotriazoline administration.

In 2 series of experiments, the experimental rats were divided into 3 groups: 1st - intact (control); 2nd - rats with acetaminophen administration within 7 days after 40-day administration of levonorgestrel and ethinylestradiol, 3rd - poisoning by acetaminophen after 40-days administration of levonorgestrel, ethinylestradiol and 7-days Thiotriazoline administration.

In 3 series of experiments, the experimental rats were divided into 3 groups: 1st - intact (control); 2nd - rats with acetaminophen administration within 7 days after 40-day administration of levonorgestrel and ethinylestradiol, 3rd - poisoning by acetaminophen after 40-days administration of levonorgestrel, ethinylestradiol and 7-days Hepadif administration.

RESULTS AND DISCUSSION. Concentration of diene conjugates decreased in blood plasma of rats with single and 7-days administration of acetaminophen after 40-days administration of estrogen and progestin and Thiotriazoline administration. Decrease intensity generation of reactive oxygen by blood mononuclear leukocytes is observed at Hepadif action, and Hepadif almost neutralized its toxic effect at seven-times administration of acetaminophen at therapeutic doses. Concentration diene (respectively 2.8 and 2.6 times), and triene conjugates (3.7 and 3.2 times) decreased in plasma of affected animals. Similarly effect was in liver homogenate.

Amount of oxidized modified proteins in blood plasma and liver of affected animals decreased at correction of lesion by Thiotriazoline and Hepadif. The administration of corrective drugs is caused decrease of malonic aldehyde concentration in plasma and liver of affected rats. Peroxidase activity in blood at correction by Thiotriazoline decreased respectively on 159 and 162% compared with affected animals. Greater effect is observed at action of Hepadif, administration of which normalizated of the peroxidase activity of blood and concentration of ceruloplasmin. Administration of Thiotriazoline and Hepadif has protective effects on glutathione system.

CONCLUSIONS. Usage Thiotriazoline and Hepadif in rats with acetaminophen toxic damage against prolonged administration of estrogens and progestins inhibit reactive oxygen species formation by mononuclear leukocytes, decreas intensity of lipid peroxidation and protein, and normalization of enzyme and nonenzyme links of antioxidant system.