It is shown that in patients with ulcer disease endogenous biosynthesis of prostaglandins E and F2α in gastric and duodenal mucosa is suppressed. In patients treated with Venter (sucralfat), ulcer healing is accompanied by enhanced prostaglandin production in both scar tissue and unaffected areas. Stimulation of prostaglandin E and F2α, synthesis in the gastroduodenal mucosa followed by activation of their cytoprotective effect in the gastrointestinal system is a key mechanism underlying the effect of Venter.

Low-molecular hydrocarbons (butan, pentan) from the exhaled air as lipid peroxidation (LPO) markers were quantified in patients with chronic diffuse liver diseases. The study was also made of microsomal oxidation enzymic activity by antipirin metabolism. The above parameters were followed up in the course of antioxidant treatment. As shown by total butan and pentan levels, LPO activity varied with the disease, being high in hepatic cirrhosis and primary biliary cirrhosis, but low in chronic active hepatitis and fat dystrophy. Increased levels of butan and pentan occurred in association with inhibited activity of P450-dependent monooxygenases. This was determined by antipirin biotransformation and confirmed by a strong inverse correlation between the amount of hydrocarbons and antipirin metabolites (4-hydroxy- and norantipirin) clearance. In the course of antioxidant therapy the most pronounced inhibiting action on formation of low-molecular hydrocarbons was distinctive of essenciale, pikamilon and copmplivit. Relevant efficacy of carsil was weaker. Similar regularity for these drugs takes place in relation to activation of microsomal oxidation.

The examination covered 52 workers engaged into production of linoleum and polyvinylchloride self-sticking coating. The workers were exposed to mixture of chemicals, especially to low concentrations of diethylhexyl phthalate (dioctyl phthalate). Detoxication in the liver was assessed through developed antipyrine test with detection of total and free derivatives of antipyrine in the urine. If compared to other functional tests, the changes in activity of enzymes dependent on cytochrome P-450 were considerably prevalent and marked. Divergent changes were seen--activated enzymes of antipyrine oxidation (I phase of the metabolism) and depression of those participating in the metabolites conjugation. The findings were considered as molecular results of toxic influence on the liver.

It is shown that in a group of animals given dioctyl phthalate alone antipyrine metabolism is enhanced (the urine content of its metabolites rises), and the histological structure of the Liver is altered by the end of the experiment: the plasmalemma membranes, the granular endoplasmic reticulum, and mitochondria are destroyed, and fat deposits are observed in the disrupted zones of the mitochondria. In animals given dioctyl phthalate and adaptogens simultaneously antipyrine metabolism normalizes, and the morphological structure of the liver changes slightly, although it does not normalize.

Examination of 42 liquidators of Chernobyl power station accident consequences, which was conducted in 5-6 years after the work in Chernobyl, proved 66.7% of examinees to have hypervolemia of hepatic circulation. These changes are due to hyperkinetic type of central hemodynamics. The data obtained prove absence of sclerotic lesions in liver.

As shown by animal experiments, low-dose trichlorodophenyl and dioctyl phthalate induce microsomal cytochrome P-450-dependent enzymes and ultrastructural changes in hepatocytes. This evidences hepatotoxicity of the compounds.

Sixty-seven participants of the elimination of Chernobyl accident sequels were examined. Of these, 30 persons (44.8%) showed normal characteristics of the three small intestinal functions studied: activity of the intestinal enzyme beta-galactosidase, motility and microbial dissemination, 23 (34.3%) deficiency of the intestinal enzyme beta-galactosidase, and 24 (35.8%) bacterial dissemination of the small intestine. In 12 persons (17.9%), the deficiency of beta-galactosidase was associated with dysbiosis of the small intestine. The incidence of hypolactasia did not exceed the characteristic typical on the whole of the population of the Moscow region.

Sixty-seven participants of the elimination of Chernobyl accident sequels were examined. Of these, 30 persons (44.8 %) showed normal characteristics of the three small intestinal functions studied: activity of the intestinal enzyme beta-galactosidase, motility and microbial dissemination, 23 (34.3 %) deficiency of the intestinal enzyme beta-galactosidase, and 24 (35.8 %) bacterial dissemination of the small intestine. In 12 persons (17.9 %), the deficiency of beta-galactosidase was associated with dysbiosis of the small intestine. The incidence of hypolactasia did not exceed the characteristic typical on the whole of the population of the Moscow region.

The comparative clinicopharmacological studies established the ability of hepatotropic agents with the membrane stabilizing properties and metabolic activity--trophopar, aika-phosphate and essential to stimulate to various degrees the processes of microsomal oxidation of antipyrine in hepatocytes at their insufficiency in patients with lesions of the hepatobiliary system of the alcohol and viral etiology. The studied drugs improve also the condition of the intrahepatic hemodynamics according to the findings of rheohepatography. The correlations between the positive dynamics of the values of antipyrine clearance, the degree of arterial blood filling (the rheographic index) and the increase of serum albumin content were found that confirms the ability of trophopar, aika-phosphate and essential to exert the complex influence on the systems and mechanisms of the realization of the liver antitoxic function.

The individual variations in the blood concentrations of gastrocepine, the period of its half-life and clearance in patients with peptic ulcers of the stomach and the duodenal bulb were determined. The patients having combined forms of peptic ulcer with chronic liver diseases exhibited most often an increase of gastrocepine half-life. A new metabolite of gastrocepine was identified by using the chromato-mass-spectral analysis. The specific antibodies to gastrocepine determining the decrease of its concentration in blood and the development of the drug resistance were found.

Guinea pigs received skin application of petroleum-derived mineral oil distillate, containing about 10% of polycyclic aromatic hydrocarbons with the 4 hours exposure time everyday during 20 days. 100% distillate preparation and it's 50%, 3% or 0.5% solutions in furfurol and ethanol are used. It resulted in the distillate-dose-dependent cytochrome P-450 induction (1.38-2.23-fold) in liver of the all exposed groups of guinea pigs and in 20-60% decrease in microsomal and cytosol glutathione transferase activities in groups which received 50% and 3% mineral oil distillate solutions. Ratio values of cytochrome P-450 content level to glutathiontransferase activity level depended linearly on the distillate doses, and it increased 2.7-4.4-fold with the distillate concentration increasing in the preparation from 0.5% to 50%. Conclusion was made that with increasing distillate doses the process of polycyclic aromatic hydrocarbon activation with the genotoxic metabolite formation predominated over the process of those metabolite detoxication.

Rats received 20 skin applications of heavy pyrolysis resin, containing about 30% of polycyclic aromatic hydrocarbons. The every exposure duration was 4 hours a day. Applications have been carried out daily 5 days a week in the course of 4 weeks. Induction of cytochrome P-450 (P-450) by 79%, significant induction of microsomal (GTm) and cytosol (GTc) glutathione-S-transferase activity (by 46 and 85%, respectively) and small increase of reduced glutathione level (by 9%) also were registered as a result of these exposures. Lipid peroxidation level determined by TBK-reactive products quantity didn't alter significantly. Close correlation between ratio values of P-450/GTm levels and P-450/GTc levels and toxic effect indices of heavy pyrolysis resin on rat immune and endocrine systems.