Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferon and interferon inducing agents depress hepatic cytochrome P-450 systems. They also induce hepatic xanthine oxidase activity. It has been suggested that free radicals produced by xanthine oxidase may cause the loss of P-450. High titers of serum interferon are induced by poly IC (poly riboinosinic acid.polyribocytidylic acid) in both C57Bl/6J and C3H/HeJ mice; Newcastle disease virus (NDV) induces a high titer of interferon in C57Bl/6J mice but not in C3H/HeJ mice. The induction of xanthine oxidase activity by NDV in C3H/HeJ mice was less than half that seen in C57Bl/6J mice, thus demonstrating a relationship between the induction of xanthine oxidase, the depression of P-450 and a genetically determined difference in responsiveness of mice to interferon inducers.
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PMID:Induction of xanthine oxidase and depression of cytochrome P-450 by interferon inducers: genetic difference in the responses of mice. 241 51

Cytochrome P-450-mediated drug biotransformation is depressed by many immune stimulants. We have shown that such depression caused by the immune stimulant dextran sulfate is mediated by Kupffer cells. The purpose of this study is to determine if other cells of the immune system or a cellular product such as interferon are involved in the depressive action of dextran sulfate on drug metabolism. Plasma samples taken from mice treated with dextran sulfate contained no detectable interferon, yet hepatic cytochrome P-450 was significantly depressed, suggesting that interferon did not mediate the depression of drug metabolism by dextran sulfate. Administration of cyclophosphamide or antilymphocyte serum to mice prior to dextran sulfate to markedly decrease lymphocyte populations did not prevent the depressive actions of dextran sulfate on cytochrome P-450, suggesting that the lymphocyte population was not involved in the dextran sulfate mediated depression. Preincubation of dextran sulfate with peritoneal macrophages prior to incubation with hepatocytes significantly depressed hepatocyte cytochrome P-450 content, while dextran sulfate alone had no direct effect on hepatocyte cytochrome P-450 content. These results further support the hypothesis that macrophages play a major role in the depression of cytochrome P-450 by dextran sulfate.
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PMID:The role of lymphocytes, macrophages and interferon in the depression of drug metabolism by dextran sulfate. 242 Jul 44

Treatment of mice with the interferon inducer polyriboinosinic acid X polyribocytidylic acid [poly(IC)] results in the depression of several hepatic proteins. In this study we examined synthesis and degradation of the proteins of liver cell organelles in mice treated with poly(IC). Effects on synthesis were determined by using [14C]- and L-[3H]leucine incorporation into control and poly(IC)-treated mice, respectively. At selected times after poly(IC) treatment the 3H/14C ratio was established for preparations of nuclei, mitochondria, lysosomes, smooth endoplasmic reticulum, rough endoplasmic reticulum, and 105,000g supernatant (cytosol). Time-dependent alterations in de novo protein synthesis were greatest in lysosomal and rough endoplasmic reticular fractions; both were depressed 9 h after treatment. The effects of poly(IC) on protein degradation were determined with [14C]bicarbonate. Poly(IC) treatment decreased the time required for disappearance of 50% of 14C-labeled protein (t1/2) of smooth and rough endoplasmic reticula. Examination of endoplasmic reticulum marker enzymes showed depression of cytochromes P-450 and b5 from 9 h onward after poly(IC) administration. Tyrosine aminotransferase activity was elevated 6 h after treatment with poly(IC), and then depressed after 9 h. The other organelle marker enzymes were not affected significantly. We conclude that poly(IC) decreases the content of proteins of the hepatic endoplasmic reticulum, including certain cytochrome P-450 isozymes, by decreasing rates of protein synthesis and increasing rates of protein degradation.
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PMID:Depression of cytochrome P-450 and alterations of protein metabolism in mice treated with the interferon inducer polyriboinosinic acid X polyribocytidylic acid. 243 May 24

The level of cytochrome P-450 and the oxidation of aminopyrine and benzo(a)pyrene hydroxylase were depressed in hepatic microsomes prepared from mice infected with the gram positive bacteria Listeria monocytogenes. Maximum depression of mixed function oxidase occurred on the 2nd day of infection. This loss in drug biotransformation capacity in the liver was correlated directly with the number of organisms found in that organ. The ability of mice to metabolize drugs in vivo also was impaired during Listeria monocytogenes infection. During the infective period the half-life of theophylline was significantly prolonged and the N-demethylation of aminopyrine as measured by the expiration of 14CO2 from radiolabeled aminopyrine was diminished. The loss of drug metabolism was not due to interferon production, fever or morphological damage to the liver. These results indicate that certain bacterial infections can depress drug biotransformation and elimination in a similar manner to that already reported in viral and parasitic infections. This finding may be of significance to patients receiving drugs which are metabolized by the mixed function oxidase system during episodes of infection with some bacteria.
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PMID:Depression of murine hepatic mixed function oxidase during infection with Listeria monocytogenes. 244 64

The purpose of this study was to determine the relative roles of viral-induced interferon (IFN) and viral infection of the liver in mouse cytomegalovirus (MCMV)-induced depression of cytochrome P-450 (cyt P-450) levels and enhancement of pentobarbital-induced sleeping time (PEN-ST). This was done by establishing the temporal relationship among the IFN response, viral infection of the liver, suppression of cyt P-450 levels, and enhancement of PEN-ST, by determining the effect of anti-IFN antibody treatment on all of these responses, and by manipulating factors known to influence viral pathogenesis and host response to virus such as animal age, virulence of the virus, and dose of virus. In general, manipulation of these factors toward increased stimulation of host immune responses resulted in greater depression of cyt P-450. The data are consistent with the hypothesis that some IFN-dependent mechanism may have contributed to the effects of MCMV infection on both cyt P-450 levels and PEN-ST; however, the temporal relationship among the various responses measured following viral infection suggested that the effect of the IFN response may be indirect and due to modulation of other host defense mechanisms. Use of anti-IFN antisera to definitively establish a role for IFN in the effects observed here proved unsuccessful. Effects on PEN-ST and cyt P-450 levels did not appear to be related to the magnitude of infection in the liver.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased susceptibility to pentobarbital following mouse cytomegalovirus infection: relative roles of viral-induced interferon and viral infection of the liver. 248 49

C3H/10T1/2 clone 8 (10T1/2) cells possess aryl hydrocarbon hydroxylase (AHH) activity capable of metabolizing polycyclic aromatic hydrocarbons to ultimate carcinogenic forms. AHH activity in 10T1/2 cells was measured before and after culturing in the presence of benzo[a]pyrene (B[a]P), and compared to the AHH activity found in carcinogen-transformed 10T1/2 cell lines treated similarly. The cell lines were also examined for B[a]P-DNA adduct formation, using the 32P-postlabelling technique. Treatment of parental 10T1/2 cells with B[a]P was found to significantly increase AHH activity and produce substantial numbers of DNA adducts. In addition to a major B[a]P-DNA adduct, 5-6 minor DNA adducts were also detected. Relative to parental 10T1/2 cells, an aflatoxin B1-transformed 10T1/2 cell line (7SA) was found to have significantly depressed AHH activity. In addition, after treatment with B[a]P, 7SA cells had only 8% of the B[a]P-DNA adduct levels found in 10T1/2 cells. This system may provide an in vitro model for investigating mechanisms responsible for the depression of cytochrome P-450 activities by chemical carcinogens.
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PMID:Induction of aryl hydrocarbon hydroxylase and DNA adduct formation in parental and carcinogen transformed C3H/10T1/2 clone 8 cells by benzo[a]pyrene. 250 24

1. In previous studies we have shown that hepatic copper and zinc increases and liver microsomal cytochrome P-450 activities greatly decreases in adjuvant arthritic rats. 2. In the present paper we study if the changes in copper and zinc could be related to depression of drug microsomal activity. Thus, the effect of in vitro addition of copper or zinc to microsomal fraction upon aminopyrine N-demethylase (AND) and aniline p-hydroxylase (APH) activity was measured. 3. Both metals produced an inhibition of enzyme activity. The reduction of AND and APH activities produced by copper (ID25 = 4.7 x 10(-5)M to AND; 1.05 x 10(-5)M to APH) was greater than that obtained with zinc (ID25 = 2.26 x 10(-4)M to AND; 3.3 x 10(-4)M to APH).
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PMID:Effects in vitro of copper and zinc on hepatic cytochrome P-450 activities. 257 90

The effects of 5-azacytidine (5-AC) administration on the hepatic cytochrome P-450 systems of mice were studied. A single i.p. dose of 5-AC (25 mg/kg) to male Swiss-Webster mice caused about a 50% depression of microsomal cytochromes P-450 and b5 and of ethylmorphine N-demethylase and ethoxycoumarin O-deethylase activities. Depression was greatest 24 h after treatment; by 48 to 72 h, cytochromes and drug metabolism had returned to near control values. Reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase activity was also depressed by 5-AC, whereas reduced nicotinamide adenine dinucleotide-cytochrome c reductase was not. Incubation of 5-AC with microsomes produced no effect on drug metabolism. The prolongation of hexobarbital sleeping time by 5-AC showed that drug metabolism is also impaired by 5-AC in vivo. These studies may have important clinical implications when certain drugs are coadministered with 5-AC.
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PMID:Depression of the hepatic cytochrome P-450 monooxygenase system by treatment of mice with the antineoplastic agent 5-azacytidine. 257 31

Administration of cysteamine to rats depressed hepatic aryl hydrocarbon hydroxylase (AHH) activity, cytochrome P-450, and total heme at 24 hr. Total heme remained decreased at 48 hr when all other parameters returned to control values. A significant 5-fold increase in heme oxygenase activity occurred in rat liver 5 hr after treatment, when AHH activity and total heme were unchanged. Histological examination of liver biopsies from rats treated with cysteamine revealed normal hepatic architecture. The observed effects of cysteamine on hepatic drug-metabolizing enzymes in vivo were not due to cysteamine-induced hepatotoxicity. Our results indicate that cysteamine increases heme oxygenase activity in rat liver, with a subsequent decrease in total heme, AHH activity, and cytochrome P-450 content. The depression of P-450 by cysteamine is likely to be an important mechanism for its protection in acetaminophen overdose. The protection studies illustrate this mechanism. Centrilobular hepatic necrosis and elevation in transaminase activity following a toxic dose of acetaminophen were prevented by treatment with cysteamine. The hepatoprotective effect of cysteamine was evident when acetaminophen was administered 24 hr after cysteamine but did not occur when acetaminophen was administered 5 hr after cysteamine or simultaneously. All groups of rats receiving cysteamine showed decreased mortality compared to the group receiving acetaminophen alone.
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PMID:The role of heme oxygenase and aryl hydrocarbon hydroxylase in the protection by cysteamine from acetaminophen hepatotoxicity. 260 41

The influence of dietary 2-acetylaminofluorene (AAF) on the cytochrome P-450 content of rat liver microsomal and nuclear fractions was immunochemically probed with monoclonal and polyclonal antibodies to cytochromes P-450c and P-450d. Cytochrome P-450d but not P-450c was immunodetected in microsomes, nuclear envelopes, and nuclei from untreated rats. The levels of both cytochromes P-450c and P-450d were elevated after a diet of either 0.1% AAF for 1 week or 0.05% AAF for 3 weeks. However, the level of cytochrome P-450c relative to P-450d was lower after the more prolonged AAF feeding. Supplementation of AAF-containing diets with 0.3% butylated hydroxytoluene (BHT), which affords protection against AAF hepatocarcinogenesis in high-fat fed rats, protected and/or induced total (spectral) nuclear envelope cytochrome P-450 content. Immunochemical studies of liver fractions showed that BHT enhanced the AAF-dependent induction of cytochrome P-450c, but not of P-450d. This was a concerted effect of AAF + BHT since dietary BHT by itself did not affect the levels of cytochrome P-450c or P-450d as compared to control rats. Since 1- to 3-week dietary AAF had little effect on total (spectral analyses) microsomal cytochrome P-450 but markedly reduced total P-450 in nuclear envelopes, the coordinated induction of specific cytochrome P-450s in the different fractions suggests selective induction and depression of different forms of cytochrome P-450 and provides additional evidence for independent regulation of the drug-metabolizing system in nuclear envelope and microsomes. In addition, these results suggest that regulation of cytochrome P-450 may play a crucial role in the nutritional modulation of AAF hepatocarcinogenesis.
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PMID:Induction of rat liver microsomal and nuclear cytochrome P-450 by dietary 2-acetylaminofluorene and butylated hydroxytoluene. 278 62


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