[The role of cytochrome p450 in metabolism of S-ethynylthiophosphates]. / Rol' tsitokhroma p450 v metabolizme S-étiniltiophosfatov.

We studied interaction between S-ethynyl ethers of phosphorus acids with cytochrome P-450 from rat liver and housefly abdomen. High thionic effect, i.e., considerable selectivity for the studied compounds in homoiotherms and arthropods, proved to the related to the triple bond in these compounds. Apparently, cytochrome P-450 participates in S-ethynylthiophosphates metabolism and breaks the P-S bond. This gives rise to "self-destroying" metabolites, namely, alkylthioketenes, which decelerate deactivation reactions through destruction of the corresponding isoform of cytochrome P-450 in the microsomal fraction in both homoiotherms and insects. However, the activation reaction goes much faster in insects than in homoiotherms.

[Enzymatic systems of insecticide detoxication in a population of Colorado beetles resistant to permethrin]. / Izuchenie fermentnykh sistem detoksikatsii insektitsidov u rezistentnoi k permetrinu populiatsii koloradskogo zhuka.

The activity of enzymes providing for permetrin detoxication in the imago resistant natural population of the Colorado potato beetle Leptinotarsa decemlineata was studied with the view of elucidating the biochemical mechanisms of resistance to the insecticide. It was demonstrated that the activity of the main enzymes of insect detoxication, i.e., microsomal monooxygenases, nonspecific esterases and glutathione-S-transferases in the permetrin-resistant population of L-decemlineata is enhanced as compared with the permetrin-sensitive population. It was demonstrated that the inhibitors of microsomal monooxygenases, piperonyl butoxide, and of nonspecific esterases, butifos, significantly increase the sensitivity of the resistant population to permetrin. The experimental results suggest that the activity of microsomal monooxygenases and nonspecific esterases is the main factor which determines the resistance of the Colorado potato beetle to permetrin.

[Changes in the activity of enzyme systems of xenobiotic metabolism at different stages of insect development]. / Izmeneniia v aktivnosti fermentnykh sistem metabolizma ksenobiotikov na raznykh stadiiakh razvitiia nasekomykh.

The cytochrome P-450 content, activity of microsomal monooxygenases, nonspecific esterases and glutathione S-transferases were studied at different stages of development of the Colorado beetle, cotton bollworm, cabbage butterfly, wax moth from the laboratory and natural populations. The data obtained demonstrate significant species, sexual and age differences in the activity of enzyme systems of insecticide detoxication. The toxic efficiency of insecticides at certain developmental stages depends on the level of activity of the enzyme systems involved in their metabolism. These data are discussed with respect to the problem of insects' sensitivity to insecticides at different developmental stages.

[The role of enzymes of xenobiotic metabolism in the resistance of insects to insecticides]. / Issledovanie roli fermentov metabolizma ksenobiotikov v rezistentnosti nasekomykh k insektitsidam.

The activity of three enzymatic systems of xenobiotic metabolism (cytochrome P-450-dependent monooxygenases, non-specific esterases and glutathione S-transferases) was studied in sensitive (S) and resistant to tetrametrin (Rtetr.), permetrin (Rperm.), mecarbenyl (Rmec.) and chlorophos (Rchlor.) strains of the housefly M. domestica L. In Rtetr. and Rmec., the activity of microsomal monooxygenases was increased 2.7- and 2.3-fold, respectively, as compared to S. The position of maxima of CO-difference spectra of cytochrome P-450 in all resistant strains (with the exception of Rchlor.) were shifted towards the short-wave region by 1-2 nm. The activity of glutathione S-transferase in Rtetr. was increased as compared to S. Analysis of the total esterase activity and electrophoresis in starch gel revealed quantitative and qualitative differences between the strains under study. In all resistant strains, except for Rmec., additional bands corresponding to the esterase activity were observed. The experimental results are discussed in terms of resistance of insects to insecticides.

[Enzyme systems of insecticide detoxication in the Colorado beetle]. / Issledovanie fermentnykh sistem detoksikatsii insektitsidov u koloradskogo zhuka.

The activity of three enzymatic systems of xenobiotic metabolism (cytochrome P-450-dependent monooxygenases, non-specific esterases and glutathione S-transferases) was studied at different stages of development of the Colorado potato beetle (Leptinotarsa decemlineata). Significant sex and ontogenetic differences in the content of cytochrome P-450, position of maxima of CO-difference spectra of the cytochrome P-450 reduced form and substrate specificity of cytochrome P-450 were revealed. The activity of non-specific esterases was shown to increase depending on the age of larvae. The insecticide 1-naphtholenol methylcarbamate which is metabolized by the system of cytochrome P-450-dependent monooxygenases is more toxic in the larvae than at the imago stage, which is correlated with the activity of this system at different stages of ontogenesis. The microsomal monooxygenase inhibitor, piperonylbutoxide, increases the insecticide toxicity in the Colorado beetle imago more than 2-fold. The experimental results testify to different contribution of the detoxication systems to the sensitivity of the Colorado beetle to insecticides at various metamorphosis stages.

[Inhibition of enzymes of insecticide detoxication in insects by an alkylating analog of a cytochrome P-450 substrate]. / Ingibirovanie fermentov detoksikatsii insektitsidov u nasekomykh alkiliruiushchim analogom substrata tsitokhroma P-450.

It was shown that the alkylating analog of cytochrome P-450 substrate - 4-bromomethyl-2,2,5,5-tetramethyl-3-imidazoline-3-oxide-1-oxyl effectively inhibits in vitro the activities of monooxygenases, glutathione-S-transferases and esterases from the abdomen of the house fly Musca domestica L. The non-alkylating analog (RH) appeared to be a very weak inhibitor of these enzymes. It was demonstrated that the inhibitory action of the alkylating analog consists in its covalent binding to the enzyme protein. Topical application of the cytochrome P-450 alkylating analog on insects led to a decrease of the enzyme activity by approximately 20%.

[Indirect method of determining drug-metabolizing enzyme activity and its clinical application]. / Nepriamoi metod opredeleniia aktivnosti fermentov, metaboliziruiushchikh lekarstvennye veshchestva, i ego primenenie v klinike.

Activity of microsomal enzymes was studied using an indirect method for estimation of the rate of antipyrine secretion with saliva in 70 healthy persons at the age from 16 to 86 years. Distinct individual differences were observed in the activity of the enzymes: time of the antipyrine half-secretion varied from 6.4 hrs to 50.1 hrs. The time of antipyrine half-secretion was significantly higher in the older (60-86 years) than in younger persons (16-30 years), suggesting decreased activity of the microsomal enzymes in older people. The microsomal enzymes activity might be increased distinctly under effect of several drugs, especially of hypotensive drugs--reserpine and dibasole. The data obtained suggest that for effective medicinal therapy it is essential to control the initial activity of microsomal enzymes as well as its alterations in the course of medicamentous treatment; the activity of microsomal enzymes in a given person must be taken into consideration for correct individual selection of doses of the drugs.

[Plasma aldosterone concentration and vascular reactivity in hypertension]. / Kontsentratsiia al'dosterona v plazme perifericheskoi krovi i sosudistaia reaktivnost' pri gipertonicheskoi bole zni.

Aldosterone concentration in peripheral plasma (radioimmune assay) and vascular reactivity (by an original tracer method) were determined in 50 patients with essential hypertension of stages I and II and in 25 healthy males. Aldosterone concentration proved to be elevated in half the patients, mostly in those with stage II of the disease. Vascular reactivity in these patients was increased and the two parameters were in good correlation. In the other group the aldosterone level and vascular reactivity were normal and there was no correlation between these two parameters. It is concluded that in some patients with essential hypertension aldosterone plays a pathogenetic role by increasing vascular reactivity.

[Use of synthetic steroids, inhibitors of microsomal enzymes, for retention of hexenal in the body and for prolongation of hexenal anesthesia under experimental conditions]. / Ispol'zovanie ingibitorov mikrosomal'nykh fermentov - sinteticheskikh steroidov - dlia zaderzhki geksenala v organizme i prolongirovaniia geksenalovogo narkoza v eksperimente

17alpha-hydroxydeoxycorticosterone and its acetate derivative inhibited the activity of rat liver microsomal enzymes. The inhibitory effect of steroids was not accompanied by induction of the enzyme synthesis, which was characteristic for the other known inhibitors of mixed function oxydases (SKF 525-A, DPEA, MPDK). These properties of the steroids suggested their use for prolongation of the effect of drugs, which are inactivated by microsomal enzymes. The suggestion was tested using hexobarbital as an example. The transformation of hexobarbital in vitro by the rat liver microsomal enzymes was completely inhibited by the equimolar amount of the steroid acetate. Treatment of rats with the steroid acetate almost doubled the life-time of the hexobarbital in rat blood and resulted in the 1.5-fold increase of the sleeping time. The most effective dose of the steroid acetate was 5 mg per 100 g of body weight, the drug being injected 15 min before hexobarbital administration.