[A selective decrease in cytochrome P450 in the liver microsomes of male rats following phenobarbital and 3-methylcholanthrene induction and acute tetrachloromethane poisoning]. / Selektivno namalenie na tsitokhrom P450 v chernodrobni mikrozomi ot muzhki plukhove sled induktsiia s fenobarbital i 3-metilkholamtren i ostra intoksikatsiia s tetrakhlormetan.

The liver microsomal content of cyt. P450 and b5 and activities of selected mixed-function oxidases were compared following phenobarbital (PB)- and 3-methylcholantrene (MC) induction and acute intoxication with carbontetrachloride (CT). PB increased the content of P450 and the activities of both NADPH-cytochrome c reductase and benzphetamin demethylase. MC increased only the content of cytochrome b5. CT after 4 hours damaged selectively the liver monoxidase components: 1. the activity of NADPH-cytochrome c reductase and the content of b5 were not changed in the three groups; 2. the content of P450 was decreased differently: more sensitive to the destructive effect of CT was the PB-inducible P450. Most resistant was the MC-inducible P450; 3. MC decreased the benzphetamin demethylation in control- and PB-microsomes in lower degree than the content of P450. The relative high rates of the benzphetamin demethylase after CT by PB-microsomes was explained by increased activity of NADPH-cytochrome c reductase in this group. The selective damaging effect of CT on P450 was interpreted by complex of local factors: metabolizing of CT to CCL3, lipid peroxidation, phospholipid microenvironment, pO2, antioxidants concentration, activity of heme degrading enzymes.

[The effect of isoniazid and lipovitan on the components of the microsomal electron-transport chains in the rat liver]. / Vliianie na izoniazid i lipovitana vurkhu niakoi komponenti na mikrozomnite elektronprenasiashti verigi ot cheren drob na plukh.

The early influence of isoniazide, used by a stomach-tube single or in combination with lipovitane, was studied on some components of electron-transporting chains in the microsomal fraction from livers of male and female rats. In comparatively unchanged amount of cytochrom P450, anilinhydroxylasic activity was increased many times in all experimental groups. This could be explained by induction of the specific isoenzyme of cytochrom P450 by isoniazide. The combination of isoniazide with lipovitane in male rats did not change the additional activity of the enzyme, but it was altered in the female rats in various directions. Isoniazide alone or with lipovitane did not change significantly N-demethylation of aminopyrine. The amount of cytochrom b5 was the same after action with isoniazide. Its combination with lipovitane in male rats reduced significantly the amount of cytochrom b5. Similar tendency in female animals was observed after usage of isoniazide during a longer interval. The reduction of cytochrom b5 was explained by a lowered inclination to lipid peroxidation due to synthesis of phosphatidylcholin, induced by lipotropic components of lipovitane. The applied doses of isoniazide were not hepatotoxic, because triacylglycerols in the serum and liver homogenate as well as nonesterified fatty acids, bilirubin and transaminase activity in serum were unchanged.

[In vitro demethylation with a NADPH-generating system containing rat cytosol enzymes]. / Demtilirane in vitro s NADF.H-generirashta sistema, sudurzhashta enzimi ot chernodroben tsitozol na plukh.

The author uses during demethylization in vitro two types of NADPH-generating systems: 1) postmitochondrial supernatant, whose disadvantage is that in vivo effects the cause for changes in demethylization could be due both to microsomes and dehydrogenases: 2) imported purified enzymic preparations, which is connected with supplying difficulties. The author proposes the usage of postmicrosomal supernatant (cytosol) from rats' liver to overcome these disadvantages. This fraction is with very good efficiency compared with that of the imported purified enzymes. The isolated cytosol, preserved at -10 degrees keeps its initial activity for a period of three days, but after or six days the diminition of the enzymic activity could be compensated by using simultaneously two substrates-isocytrate and glucose-6-phosphate for demethylizating systems.

[Early effect of adrenalectomy and castration on the demethylating activity of the liver microsomal fraction in male rats]. / Ranen efekt na adrenalektomiiata i kastratsiiata vurkhu demetilirashtata aktivnost na chernodrobna mikrozomna fraktsiia ot muzhki plukhove.

The author examines three indices in liver microsomal fraction during the first five days after castration and adrenalectomy of male rats: demethylation in vitro of amidophen, amount of cytochrome P450 and cytochrome b5. Demethylating activity is lowered significantly to the respective control on the second day after adrenalectomy--73%, on the fifth day--61%; after castration on the third day--71%, on the fifth day--75%; after simultaneous castration and adrenalectomy after two days--53%, but on the fifth day--22%. The amount of cytochrome P450 diminishes parallely to the demethylating activity is due to the reduced amount of cytochrome P450, but the reduction of the latter is explained by the lowered activity of aminolevulanatsynthetase--the limiting enzyme in the synthesis of heme of cytochrome P450. Androgens and corticoids are inductors of microsomal oxidative enzymes and probably on the basis of this action the activity of aminoevulinatsynthetase is affected.

[Standardized system for incorporating labelled amino acid in vitro with rat spleen fractions]. / Standartizirana sistema za vkliuchvane na beliazana aminokiselina in vitro s fraktsii ot slezka na plukh

The authors describe a standardized system devoid of cells with polyribosomes and total cellular juice, obtained from a rat spleen. They discuss the dependence between incorporating capability and the temperature of incubation, concentration of magnesium ions as well as the significance of single components for the optimal capacity of the incorporating system.