Possible mechanisms responsible for the effect of dimedrol on nonsynthetic biotransformation of xenobiotics in rat liver

The ability of dimedrol to inhibit o-demethylation of paranitroanisole, which in rat liver is catalyzed by cytochrome P-450, is demonstratedin vivo andin vitro. The affinity of dimedrol for cytochrome P-450 is higher than that of other xenobiotics. It is suggested that the effect of dimedrol on the metabolism of paranitroanisole and some other xenobiotics is realized during formation of the enzyme—substrate complexes between these substances and cytochrome P-450. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 9, pp. 301–304, September, 1997     

Role of lipoproteins transporting lipophilic xenobiotics in the induction of microsomal monooxygenases

We studied the effects of lipopolysaccharide on activity of liver microsomal enzymes against the background of xenobiotics treatment. Against the background of lipopolysaccharide stimulation of macrophages we observed in vivo activation of cytochromes P-450 1A subfamily in liver microsomes with Arochlor 1254, but not induction of cytochrome P-450 2B subfamily with phenobarbital.     

Hydroxylation of xenobiotics and steroids in the endoplasmic reticulum of the rat liver

A polarographic method is suggested and can be recommended as a simple device for measuring the rates of oxidation of steroid hormones and xenobiotics. The rate of hydroxylation of steroids depends, it is suggested, on the polarity of the molecule of the oxidation substrate.Department of Molecular Pharmacology and Radiobiology, Medico-Biological Faculty, and Central Research Laboratory, N. I. Pirogov Second Moscow Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. A. Pokrovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 3, pp. 299–301, March, 1976.     

Adaptogen ADAPT modulates stress-induced HSP70 synthesis and improves organism's resistance to heat shock

The effect of the herbal adaptogen ADAPT on the basal and heat shock-induced synthesis of HSP70 and organism's resistance to heat shock is studied. It is shown that ADAPT decreases accumulation of these proteins in the myocardium and promotes their accumulation in the liver. ADAPT has no effect on arterial pressure but prevents its drop induced by heat shock and markedly increases the survival rate of experimental animals. These data agree with the hypothesis that the effect of ADAPT on the synthesis of HSP70 is an important component of its protective action. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 6, pp. 629–631, June, 1997     

Rat model of acute tetracycline hepatosis and its dynamic predictors

It is demonstrated that intraperitoneal administration of tetracycline hydrochloride in a dose of 125 mg/kg leads to the development of acute fatty hepatosis in rats within a 24-h period, by which time the maximum accumulation of lipids and triacylglycerides is observed in the liver. In addition, a direct dependence is established between the severity of fatty hepatosis and a decrease in the cytochrome P-450 content. The cytochrome P-450 content is a dynamic predictor of tetracycline fatty hepatosis. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 12, pp. 603–605, December, 1994     

Two-step activation of valproic acid (VPA) by hepatic cytochrome P-450

There is now considerable evidence that the unsaturated metabolite of VPA, delta 4-VPA, may be responsible for VPA-induced hepatic injury. It is proposed that VPA is activated to a hepatotoxic species by a two-step cytochrome P-450-mediated mechanism consisting of 1) desaturation and 2) unknown activation, possibly by epoxide formation, involving one or more P-450 isozymes with subsequent covalent binding to cellular macromolecules. In vivo and in vitro experimental protocols are indicated for testing the proposed hypothesis.     

In vivo measurement of velocity profiles in arterioles

Measurements of velocity profiles in arterial microvessels (20–103 μ in diameter) of rat mesentery and m. creamaster showed that bloodflow regimen under natural conditions can be similar to that of Newton fluid or pseudoplastic laminar stream, which indicates significant fluctuations in blood viscosity. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 12, pp. 707–709, December, 2006     

Heat shock protects endotheliocyte actin cytoskeleton from destruction under conditions of ATP depletion: Role of heat shock protein HSP27

Heat shock followed by 12–18-hour recovery induced tolerance of cultured endothelial cells to ATP depletion preventing degradation of actin filaments and HSP27 dephosphorylation/redistribution. HSP27 accumulates during this period, while inhibition of protein synthesis abolishes the protective effect of heat shock. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 2, pp. 237–240, February, 1999     

Dysfunction and correction of microsomal enzyme oxidation, glucuronidation and glutathione conjugation of xenobiotics in the liver of deoxycholate-intoxicated rats

Intoxication with deoxycholic acid is accompanied by destruction of hepatocyte plasma membrane (increased serum alanine aminotransferase activity) and inhibition of monooxygenase, glucuronidase and glutathione systems of rat liver. Heptral and cordiamine (mitethamide) had no effect on membrane integrity, while α-tocopherol and ursofalk (ursodeoxycholic acid) protected membranes. Ursofalk and cordiamine are superior a α-tocopherol and heptral by their ability to activity of monooxygenase, glucuronidase, and glutathione conjugating systems in the liver. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 1, pp. 56–60, January 2000     

Protective hepatotropic effect of preparations from mytilidae and ginseng in animals given dioctyl phthalate

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. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 5, pp. 550–554, May, 1994 Presented by N. F. Izmerov, Member of the Russian Academy of Medical Sciences     

Immunohistochemical localization of cytochrome P-450

Institute of Pediatrics, Eastern Siberian Branch, Academy of Medical Sciences of the USSR, Irkutsk. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 112, No. 12, pp. 646–647, December, 1991.     

Effects of phospholipid-containing hepatoprotectors on cytochrome P-450-dependent antitoxic function of the liver during experimental toxic hepatitis

Phospholipid-containing hepatoprotectors essentiale and eplir inhibited conversion of cytochrome P-450 into cytochrome P-420 and restored aminopyrine N-demethylase and anilinen-hydroxylase activities of cytochrome P-450 in rats during acute hepatitis induced by CCl₄ and allyl alcohol. The polyphenol phytopreparation legalon did not prevent degradation of cytochrome P-450. Differences in the effects of hepatoprotectors on the impaired antitoxic function of the liver are probably associated with the abilities of essentiale and eplir to provide phospholipids for regeneration of endoplasmic reticulum membranes of hepatocytes. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 4, pp. 392–394, April, 1999     

Correction of dysfunction of enzyme systems of microsomal oxidation, glucuronidation, and glutathione conjugation of xenobiotics in the liver of rats with deoxycholate intoxication

Intoxication with deoxycholic acid disturbed the integrity of hepatocyte plasma membranes (elevation of alanine transaminase activity in the plasma) and inhibited the monooxygenase, glucuronosyltransferase, and glutathione S-transferase systems in rat liver. Heptral and cordiaminum did not affect the integrity of plasma membranes, while α-tocopherol and, especially, ursofalk produced membrane-protective effects. Ursofalk and, especially, cordiaminum are far superior to α-tocopherol and heptral in their ability to normalize functions of the monooxygenase, glucuronosyltransferase, and glutathione S-transferase systems in rat liver. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 3, pp. 297–301, March, 2000     

Activity and inducibility of cytochrome P-450-1A in the liver of mice with different sensitivity to hepatocarcinogenic effect of o-aminoazotoluene

Specific activity of cytochrome P-450-1a is detected in the liver of 7 inbred mouse strains sensitive (SWR, C3HA, DD, and CBA) and resistant (AKR, CC57BR, and C57BL) to o-aminoazotoluene-induced hepatocarcinogenesis: 7-ethoxyresorufin-O-diethylase and 7-methoxyresorufin-O-dimethylase, induced by benzo(a)pyrene and o-aminoazotoluene. Mice sensitive (CC57BR and C57BL) and resistant (AKR) to P-450-1a induction were resistant to induction of liver tumor and, similarly, mice both resistant (SWR and DD) and sensitive (C3HA and CBA) to P-450-1a induction were sensitive to hepatic tumor induction. Therefore, there was no correlation between inducibility of cytochrome P-450-1a and sensitivity to o-aminoazotoluene-induced hepatocarcinogenesis at the initial stages of chemical carcinogenesis. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 8, pp. 201–203, August, 1998