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1.
Summary Streptozotocin-diabetes in rats leads to a decrease of cytochrome P-450 UT-A (the major form in control rats) and an increase of cytochrome P-450 PB-B (the major one induced by phenobarbital treatment) in liver microsomes. The increased benzphetamine-N-demethylase activity can be related to the induction of cytochrome P-450 PB-B.  相似文献   

2.
We evaluated the effect of hypoxia (7% v/v) on hepatic heme turnover in vivo and microsomal heme protein content in male Sprague-Dawley rats. Hepatic heme protein turnover, measured as 14CO-production during continuous infusion of 5-14C-aminolevulinic acid, a precursor of nonerythrogenic heme, was decreased 60% during hypoxia and returned to control levels promptly after reoxygenation. Hepatic cytochrome P-450 content was decreased in hypoxic and 24-h reoxygenated animals. We conclude that normobaric hypoxia decreases hepatic cytochrome P-450 which could contribute to decreased drug metabolism in hypoxia. This decrease is probably due to heme oxygenase-independent breakdown of hepatic heme.  相似文献   

3.
Summary We evaluated the effect of hypoxia (7% v/v) on hepatic heme turnover in vivo and microsomal heme protein content in male Sprague-Dawley rats. Hepatic heme protein turnover, measured as14CO-production during continuous infusion of 5-14C-aminolevulinic acid, a precursor of nonerythrogenic heme, was decreased 60% during hypoxia and returned to control levels promptly after reoxygenation. Hepatic cytochrome P-450 content was decreased in hypoxic and 24-h reoxygenated animals. We conclude that normobaric hypoxia decreases hepatic cytochrome P-450 which could contribute to decreased drug metabolism in hypoxia. This decrease is probably due to heme oxygenase-independent breakdown of hepatic heme.  相似文献   

4.
Immunomodulating lipopeptides lauroyl-L-Ala-gamma-D-Glu-LL-A2pmNH2-Gly (RP 44.102) and lauroyl-L-Ala-gamma-D-Glu-LL-A2pmNH2 (RP 56.142) were found to protect mice against the hepatotoxicity of paracetamol, which is due to cytochrome P-450 dependent formation of toxic metabolites and radicals. In fact they decreased the amount of hepatic microsomal cytochrome P-450, and the level of CCl4-induced lipid peroxidation. In contrast lauroyl-L-Ala-gamma-D-Glu-DD-A2pmNH2 (RP 53.204), which only differs by the configuration of the two chiral carbons of A2pm (diaminopimelic acid) and is not an immunomodulating agent, failed to protect against poisoning by paracetamol and had no effect on the level of hepatic cytochrome P-450 or the microsomal CCl4-induced lipid peroxidation. This provides a clear connection between the immunostimulating properties of a compound and its effects on xenobiotic biotransformations.  相似文献   

5.
Summary Intravenously administered light lanthanons change spectral interactions in rat liver not only by decreasing the concentration of cytochrome P-450, but they also cause a qualitative change in the cytochrome P-450 molecule or its microenvironment.P. Arvela is a fellow of the Alexander-von-Humboldt-Stiftung.  相似文献   

6.
Summary The effect of fenarimol, a pyrimidine-containing cytochrome P-450 inhibitor, was tested in vitro on brain-ring gland complexes ofCalliphora vicina (Dipt., Calliphoridae), and on microsomes prepared from the fat body of 0-h wandering stage larvae ofNeobellieria bullata (Dipt., Sacrophagidae). Fenarimol had no influence on the formation of ecdysone, but it was an effective inhibitor of cytochrome P-450-dependent ecdysone 20-monooxygenase.  相似文献   

7.
Summary The injection of testosterone propionate for 4 successive days into female rats resulted in an increase of the in vitro conversion of the hydroxylated testosterones from testosterone by the hepatic microsomal, fraction, but no change in the content of microsomal cytochrome P-450 occurred. Actinomycin D or puromycin, which was administered for 4 days with injections of testosterone propionate, prevented the enzyme induction.  相似文献   

8.
Summary The alkaloid sanguinarine reported to be responsible for several outbreaks of epidemic dropsy in the tropics was examined for its hepatotoxic potential in rats. The studies showed that a single i.p. dose (10 mg/kg) of sanguinarine not only increased the activity of SGPT and SGOT substantially but also caused a significant loss of microsomal cytochrome P-450 and benzphetamine N-demethylase activity. Furthermore, the treated rats exhibited considerable loss of body and liver weight, peritoneal edema and slightly enlarged livers with fibrinous material. Microscopic examination of the liver tissue showed progressive cellular degeneration and necrosis further substantiating that sanguinarine is a potential hepatotoxic alkaloid.  相似文献   

9.
R R Dalvi 《Experientia》1985,41(1):77-78
The alkaloid sanguinarine reported to be responsible for several outbreaks of epidemic dropsy in the tropics was examined for its hepatotoxic potential in rats. The studies showed that a single i.p. dose (10 mg/kg) of sanguinarine not only increased the activity of SGPT and SGOT substantially but also caused a significant loss of microsomal cytochrome P-450 and benzphetamine N-demethylase activity. Furthermore, the treated rats exhibited considerable loss of body and liver weight, peritoneal edema and slightly enlarged livers with fibrinous material. Microscopic examination of the liver tissue showed progressive cellular degeneration and necrosis further substantiating that sanguinarine is a potential hepatotoxic alkaloid.  相似文献   

10.
Summary Immunomodulating lipopeptides lauroyl-L-Ala--D-Glu-LL-A2pmNH2-Gly (RP 44.102) and lauroyl-L-Ala--D-Glu-LL-A2pmNH2 (RP 56.142) were found to protect mice against the hepatotoxicity of paracetamol, which is due to cytochrome P-450 dependent formation of toxic metabolites and radicals. In fact they decreased the amount of hepatic microsomal cytochrome P-450, and the level of CCl4-induced lipid peroxidation. In contrast lauroyl-L-Ala--D-Glu-DD-A2pmNH2 (RP 53.204), which only differs by the configuration of the two chiral carbons of A2pm (diaminopimelic acid) and is not an immunomodulating agent, failed to protect against poisoning by paracetamol and had no effect on the level of hepatic cytochrome P-450 or the microsomal CCl4-induced lipid peroxidation. This provides a clear connection between the immunostimulating properties of a compound and its effects on xenobiotic biotransformations.  相似文献   

11.
G R Jones  R Thatcher 《Experientia》1985,41(8):1045-1046
Disturbance to energy production in the S180 sarcoma (CB) by optical isomers of isoproterenol was assessed from altered adenine nucleotide levels at 1 h. The L-isomer almost halved the ATP level and lowered the energy charge significantly; the D-isomer was inactive. Dependence of tumor injury on cytochrome P-450 activity appears unlikely.  相似文献   

12.
Endogenous inhibitor of ecdysone synthesis in crabs   总被引:1,自引:0,他引:1  
Attempts to isolate the molt-inhibiting hormone (MIH) of crustaceans from crab eyestalks (ES) resulted in the characterization of xanthurenic acid as an inhibitor of ecdysone biosynthesis in the cultured Y-organ-complex (YOC) homogenate. It was also found that 3-hydroxy-L-kynurenine present in the ES is transformed into xanthurenic acid in the YOC and body fluid. Its mode of inhibitory action in ecdysone biosynthesis is probably inactivation of cytochrome P-450.  相似文献   

13.
Summary Fe2+, Fe3+ and their complexes with EDTA and hemin, methemalbumin and methemoglobin were active catalyzers of H2O2 supported styrene oxidation to styrene oxide. Methemoglobin was the most active compound; its peroxidative activity was comparable to that of cytochrome P-450 in liver microsomes of phenobarbital-treated rats. Cumene hydroperoxide supported styrene oxidation with methemoglobin and microsomal hemoproteins and was found to be more efficient than H2O2.This work was supported by C.N.R. (National Research Council) contract No. 79.03197.04.  相似文献   

14.
Dinemorphan, an antitussive drug, is N-demethylated in vitro by mouse liver microsomes with biphasic kinetics showing two apparent Km and Vmax. Moreover, dinemorphan N-demethylation is inhibited by CO, SKF-525A, metyrapone and it is specifically catalyzed by a phenobarbital-inducible form of cytochrome P-450.  相似文献   

15.
M J Mitchell  S L Smith 《Experientia》1988,44(11-12):990-991
The chitin synthetase inhibitor plumbagin and its 2-demethyl derivative juglone were found to inhibit in a dose-response fashion the cytochrome P-450 dependent ecdysone 20-monooxygenase activity associated with adult female Aedes aegypti, wandering stage larvae of Drosophila melanogaster, and fat body and midgut from last instar larvae of Manduca sexta. The concentration of these naphthoquinones required to elicit a 50% inhibition of the steroid hydroxylase activity in all the insects was approximately 1 x 10(-4) M.  相似文献   

16.
The adenylate cyclase activator forskolin and its pharmacologically inactive derivative 1,9-dideoxyforskolin were found to inhibit in a dose-dependent fashion the ecdysone 20-monooxygenase activity associated with wandering stage larvae of Drosophila melanogaster and fat body and midgut from last instar larvae of the tobacco hornworm, Manduca sexta. The concentrations of these labdane diterpenes required to elicit a 50% inhibition of the cytochrome P-450 dependent steroid hydroxylase activity in the insect tissues ranged from approximately 5 x 10(-6) to 5 x 10(-4) M.  相似文献   

17.
Summary Organic dyes such as malachite green, methylene blue, fuchsin, safranine T, neutral red, phenazine methosulphate, riboflavin, dichlorophenolindophenol, phenolphthalein, and fluorescein, inhibit hepatic microsomal mixedfunction oxidases and, partly, enhance, partly, inhibit hepatic microsomal NADPH-dependent cytochrome c and neotetrazolium reductases, in contrast to other inhibitors of drug metabolism which do not affect cytochrome c reductase but only interact with cytochrome P-450.Dedicated to Prof. G. Pfleiderer on the occasion of his 60th birthday.Acknowledgment. The author thanks Mrs Fey, Mrs Meier, and Mr Weinrauch, for their skilful technical assistance; he is grateful to Dr A. Sinharay (Hoechst AG) for providing him with anisic ester and methylayapanine.  相似文献   

18.
Summary Oral administration of cadmium to female rats for 6 weeks does not reduce the microsomal cytochrome P450 levels in the liver and kidneys, nor the cytochrome P450 content in the renal mitochondria.  相似文献   

19.
M Younes 《Experientia》1985,41(4):479-481
Superoxide dismutase, catalase and methional proved capable of inhibiting the microsomal oxidation of thiobenzamide, which is most probably catalyzed by the flavin-containing monooxygenase. This indicates that excited oxygen species (e.g. X O-2,H2O2, X OH) are involved in the catalytic cycle of this enzymatic reaction. CO, which inhibits the cytochrome P-450-dependent oxygen radical formation, had no effect on the oxidation reaction, suggesting that the source of the reactive oxygen species is not the microsomal mixed-function oxidase.  相似文献   

20.
Summary Systemic action of nicotinamide significantly alters the activities of hepatic drug metabolizing enzymes. Male rats injected with nicotinamide have reduced levels of cytochrome P450, demethylases and aniline hydroxylase. The changes appear to be sex-dependent since in the case of female rats activities of p-nitroanisole-o-demethylase and aniline hydroxylase are enhanced whereas cytochrome P450 content remains unaltered.Authors gratefully acknowledge the encouragement given by Professor A.S. Paintal during the course of this investigation. One of us (J.K.B.) is grateful to the Council of Scientific and Industrial Research, New Delhi, for the award of a research fellowship.  相似文献   

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