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Antiviral and interferon inducing activity of the amixine and its some derivatives, as well as their influence on the proteolytic enzymes activity, monooxygenase activity of the microsomal fraction, level of the lipids peroxidation were studied. Lack of correlation between antiviral and interferon inducing activity in the investigated series of compounds was found. Vice versa, the good correlation between interferon inducing activity and the elastase-like activities inhibition ability of the compounds was observed. It allows to state the assumption, that only one ability of compounds to induce of an interferon doesn't suffice for obtaining of high titres of interferon, and while their rather high antiproteolitic activity is necessary. It's shown, that except for one compound the influence of amixine and its derivatives on the red-ox enzymes activity well correlates with their ability to the interferon-inducing. All presented above allows to attribute amixine and its derivatives to polymodal antiviral agents.

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Effect of preliminary intraperitoneal injection on the state of the glutathione system and lipid peroxidation intensity in the lungs of rats subjected to NO2 has been studient. This compound is shown to decrease significantly all lipid peroxidation processes and to inhibit completely glutathion oxidation. These effects are supposed to be a result not only of antioxidant properties of enomelanin, but also of its ability to promote a decrease in the activity of glutathione-depending enzymes subjected to NO2.

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Prophylactic injection of enomelanine has been studied for its effect on hemic hypoxia and on different parts of breathing system. The enomelanine was shown to be effective for decreasing the level of carboxyhemoglobin and for protection from succinate dehydrogenase and cytochromoxidase. The authors think that these effects of enomelanine are conditioned not only by its anti-hypoxia abilities, but also by the capacity to activate the alternative protective mechanisms of the cell.

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It has been studied how preventive administration of EDTA influences toxic NO2- induced pulmonary edema and disturbances in antioxidant systems. The compound in question, being preventively administered, has exerted a significant antiedematic effect as a result of a decrease in lipid peroxidation intensity and protection of the most important substrate components of the nonenzymatic antioxidant system from the oxidation effect.

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Influence of intraperitoneal administration of polygalacturonic acid derivatives at a dose of 100 mg/kg on the glutathione system and lipid peroxidation in the rat lung after treatment with NO2 was studied. A considerable decrease of lipid peroxidation intensity by these derivatives was caused not only by ability of these compounds to the chelate formation and absorption of free radicals, but also by the substantial activation of the glutathione system.

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Natural porphyrin (hemin and its synthetic analogue--tetraphenylporphyrin with iron TPP-Fe3+) has been studied for its effect on activity of monooxygenase responses and cytochrome P-450 content against a background of introduction of four-chlorine carbon in the in vitro experiments. The reducing effect of hemin and TPP-Fe3+ on cytochrome P-450 and dependent enzymes: N-demethylase, n-hydroxylase and benz(a)pyrene hydroxylase has been noticed; the synthetic analogue of heme was more efficient.

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Modifying effects of widely used immunomodulator tylorone on lipid peroxidation and the state of antioxidant system were studied under conditions of normal state as well as in subacute poisoning with carbon monooxide. Multiple effects of tylorone on these reactions were found in various tissues. The drug increased content of reduced glutathione in liver tissue, while amount of the substance was decreased in kidney and heart muscle. Content of diene conjugates and of SH-groups in blood, content of ascorbate in adrenal glands and activity of glucose-6-phosphate dehydrogenase in liver tissue were found to decrease. After administration of tylorone alterations of the most patterns studied under hypoxic conditions were similar to those of normal state. At the same time, the oppositely directed alterations were detected in content of reduced glutathione in heart muscle and in activity of glucose-6-phosphate dehydrogenase in liver tissue under conditions of carbon monoxide poisoning.

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TPP-Sn4+ was administered intraperitoneally (25 mg/kg body weight). The study was performed for 1-30 days. A day after administration the increase in the hemoprotein level 1.4 times was observed, as well as an increase in the level of p-hydroxylation of aniline. On 7-14 days the greatest increase in cytochrome P-450 content was observed. To clarity the mechanism of TPP-Sn4+ effect on cytochrome P-450, we studied its effect on the activity of heme oxygenase and LP rate. This compound is an inhibitor of heme oxygenase activity and reduces the rate of LP in the microsomes which regulates porphyrin metabolism in the organism.

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Tetraphenyl porphyrin (TPP) and its complexes with Fe3+, Co2+, Cu2+, Zn2+ and Ni2+ inhibited cytochrome P-450-dependent enzymes in rat liver microsomes. Content of cytochrome P-450 was decreased by 27% or 49% depending on the substance administered (TPP or its metal complexes, respectively). N-demethylase was inactivated by about 30%; the rate of aniline p-hydroxylation was decreased by 30-45% depending on the type of the metal complex. But these substances did not affect practically the benz(alpha)pyrene hydroxylase activity. The inhibitory effect of TPP of its metal complexes appears to occur due to activation of lipid peroxidation and of hemoxygenase, which is responsible for biodegradation of hem in cytochrome P-450.

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It is shown that tetraphenylporphyrin (TPP) and its complexes with metals decrease the rate of the diene conjugate formation. The above compounds increase the malonic dialdehyde accumulation. The effect of TPP and its complexes with metals is connected with stimulation of lipid peroxidation in biomembranes.

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The experimental data on the role of cytochrome P-450 in the metabolism of arachidonic acid and protanoids in different organs and tissues are analyzed. This system is considered from the standpoint of the possibility to participate in the synthesis of primary prostaglandins. A conclusion is drawn that cytochrome P-450 takes an active part not only in oxidation of different xenobiotics and steroid hormones but also in the synthesis and decomposition of prostaglandins--the most important cell regulators.

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The kinetic parameters of two monoxygenase (N-demethylase and benzo(a)pyrene hydroxylase) reactions occurring in murine immunocompetent cells were determined. It was shown that the pH optimum for macrophage enzymes lies at 7.4, whereas that for thymocytes and spleen cells at 8.5. The effects of cytochrome P-450 inhibitors (methyrapone, SKF-525A, tilorone) on monooxygenase systems of immunocytes were investigated. Methyrapone and SKF-525A were shown to be effective inhibitors of N-demethylase. The mode of inhibition changes from non-competitive to competitive, depending on the inhibitor concentration. Tilorone, an immunostimulator and inhibitor of liver cytochrome P-450-dependent enzymes, competitively inhibits N-demethylase and benzo(a)pyrene hydroxylase of immunocytes.

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The phytohemagglutinin effect in vivo on monooxygenase activity depends on the type of the cells under study (thymocytes, splenocytes, macrophages, hepatocytes) and on the period after lectin injection. Variations of monooxygenase activities associated with different forms of cytochrome P-450 are established to have a number of peculiarities in isolated hepatocytes as compared to those in the liver microsome fraction. These differences are supposed to be due to the effect of nonmicrosomal cytochrome P-450. The results obtained are discussed with regard for phytohemagglutinin effect on systems regulating activity of cytochrome P-450-dependent monooxygenases.

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The activity of flavoproteid-dependent monooxigenase (benzpyrene-3-monooxigenase) in thymocytes, splenocytes and macrophages was studied in dynamics of development of the immune response to ram erythrocytes and with administration of low-molecular immunodepressants and immune stimulators to mice. It is shown that primary and secondary immunizations decrease the enzyme activity in splenocytes and macrophages. In the thymus cells it grows thrice as high a day after the antigen administration and then lowers. It is supposed that stimulation at the initial stages of the monooxigenase activity in the thymus and its inhibition in splenocytes and macrophages are main stages in development of the immune response. The data obtained are discussed accounting for cytochrome P-450 participation in metabolism of endogenic steroids and prostaglandins which are immunogenesis regulators.

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Activity of mice hepatocyte monooxygenases was studied in dynamics of immune response to administration of sheep erythrocytes and phytohemagglutinin. During the primary and secondary immune response the antigen inhibited activity of cytochrome P-450-dependent reactions (N-demethylase and p-hydroxylase), which was apparently due to synthesis of interferon. At the same time, activity of cytochrome P-448-dependent system (benz-alpha-pyrene hydroxylase) was 1.5-5-fold increased as compared with controls as a result apparently of its participation in synthesis of immunoregulators.

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