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)

This study was designed to measure the interaction of 8 weeks of endurance running and chronic ethanol consumption upon skeletal muscle mitochondria. Male Sprague-Dawley rats were assigned to 1 of 4 groups; ethanol diet sedentary (SED-E), ethanol diet trained (RUN-E), control diet sedentary (SED-E), and control diet trained (RUN-C). The ethanol groups, SED-E and RUN-E, consumed 35% of their calories as ethanol in a liquid diet. The trained groups, RUN-C and RUN-E, ran 5 days/wk for 8 weeks and were running 30 m/min for 90 min/day by the last week. The SED-E group had significantly lower body weights and gastrocnemius-plantaris weights than did the other 3 groups. The left ventricular heart weights showed no treatment effects. Mitochondrial respirations and cytochrome content were significantly depressed in the SED-E group and significantly elevated in the RUN-C and RUN-E groups. Two conclusions can be drawn from these data; (1) the ethanol diet caused a depression in mitochrondrial function of skeletal muscle, in weight gain, and in gastrocnemius-plantaris muscle mass amd (2) an endurance running program offset the deleterious effects of ethanol in all of these areas.
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PMID:The interaction of endurance running and ethanol on skeletal muscle mitochondria. 719 7

Cells of Saccharomyces carlsbergensis 4228 grown aerobically with added thiamine (1 microgram . ml-1) in a vitamin B6-free medium contained no detectable heme precursors, such as delta-aminolevulinate, coproporphyrin III, or protoporphyrin IX. The deficiency in heme precursors in the thiamine-grown cells was accompanied by previously reported phenomena, i.e., growth depression, vitamin B6 deficiency, and respiratory deficiency due to a marked decrease in the activities of heme-containing enzymes and cytochrome level (I. Nakamura et al., FEBS Lett. 62: 354-358, 1976). It has been reported that all of the effects of thiamine are abolished by adding pyridoxine to the medium. delta-Aminolevulinate was found to have quite similar effects to those of pyridoxine, except that growth was partially improved by delta-aminolevulinate, whereas it was fully restored by pyridoxine. Incubation of the thiamine-grown cells with delta-aminolevulinate resulted in the appearance of the heme precursors and the heme-containing enzymes. Consistent with the lowered amount of vitamin B6, the thiamine-grown cells had a lowered activity of delta-aminolevulinate synthase, a pyridoxal phosphate-dependent enzyme. Not only the holoenzyme activity but also the apoenzyme activity was very low in these cells. These results indicate that the thiamine-induced vitamin B6 deficiency brings about the decrease in delta-aminolevulinate synthase activity, which leads to heme deficiency and therefore to respiratory deficiency.
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PMID:Mechanism of thiamine-induced respiratory deficiency in Saccharomyces carlsbergensis. 727 38

Interferon and interferon inducers are well known to depress hepatic cytochrome P-450 (P-450). Previous reports have suggested that all constitutive members of the P-450 family of proteins are affected in this manner, whereas inducible P-450s--including cytochrome P-4503A1 (CYP3A1)--are resistant to the effects of interferons. We examined the effect of interferon [produced in response to polyinosinic acid-polycytidylic acid (polyIC; 10 mg/kg) administration] on the induction of CYP3A1 in the female rat by the macrolide antibiotic troleandomycin (TAO; 200 mg/kg), and the antiglucocorticoid pregnenolone-16 alpha-carbonitrile (PCN; 300 mg/kg). The induction of CYP3A1 was characterized by erythromycin N-demethylation, Western blotting, and mRNA quantitation with a specific oligonucleotide cDNA probe. PCN-mediated induction of erythromycin metabolism was depressed by 85% following polyIC administration. PolyIC depressed the induction of CYP3A1 apoprotein by TAO (84%) and PCN (73%). The depression of enzyme activity and protein were accompanied by a corresponding decrease in hepatic CYP3A1 mRNA. It is concluded that CYP3A1 is sensitive to the depressant effects of interferon, and that interferon appears to act at a pretranslation step that is independent of the induction process per se.
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PMID:Modulation of rat hepatic CYP3A1 induction by the interferon inducer polyinosinic acid-polycytidylic acid (polyic). 768 58

Biochemical and histochemical studies were conducted in aflatoxin B1-induced liver tumors in adult rainbow trout. Specific activities of the phase I enzymes, ethoxyresorufin-O-deethylase (EROD), microsomal and cytosolic epoxide hydrolase (mEH and cEH), aldehyde dehydrogenase (ALDH) and DT-diaphorase, and the phase II enzymes, gamma-glutamyltransferase (gamma-GT), glutathione transferase (GST) and uridine diphosphoglucuronyl transferase (UDPGT) were measured. Cryostat sections of tumor and surrounding liver from the same cohorts were analyzed immunohistochemically for cytochrome P450IA1 and histochemically for ALDH (benzaldehyde and hexanal), DT-diaphorase, gamma-GT and uridine diphosphoglucuronyl dehydrogenase (UDPGdH). In tumor tissues, the largest biochemical changes were found with benzaldehyde dehydrogenase, where activity increased from undetectable levels to 7.4 nmol/min/mg protein, and gamma-GT, where activity increased 12-fold over controls. Increases in other enzymes ranged from 1.26 to 2.84 times that of control liver, except EROD, which decreased, and cEH and mEH, which were unchanged. Histochemical analyses showed the induction of ALDH, gamma-GT, DT-diaphorase and UDPGdH, and the depression of cytochrome P450IA1 in hepatic neoplasms. In addition, marker enzyme histochemistry of neoplasms revealed heterogeneous populations of hepatocytes and absence of necrotic areas.
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PMID:Biochemical and histochemical properties of hepatic tumors of rainbow trout, Oncorhynchus mykiss. 809 46

Anthraquinone dyes are utilized by the military in colored-smoke grenades. During production, workers in munitions plants may be exposed to fugitive emissions of these dyes or mixtures thereof. The effects of a prototype violet dye mixture (VDM) consisting of Disperse Red 11 (DR11), [1,4-diamino-2-methoxy-anthraquinone] and Disperse Blue 3 (DB3) [1-methylamino-4-hydroxyethylamino-anthraquinone] on F344 male and female rats have been investigated. Acute 1-day inhalation exposures (6 hr) to VDM were conducted at 1000, 300, 100, 70, 40, and 10 mg/m3, with an additional exposure to 40 mg/m3 6 hr/day for 5 days; 4.22 +/- 2.1 microns (MMAD +/- delta g). Lung burdens of dye, general histopathology, and/or liver function were evaluated at 0, 3, and 7 days postexposure. Unexpected lethality due to severe liver damage was observed with acute exposures of > or = 300 mg/m3 and in the 5-day 40 mg/m3 exposures. Centrilobular degeneration and necrosis of liver cells was concentration-dependent with inhalation of VDM > or = 40 mg/m3. In addition, nasal olfactory epithelium exhibited degeneration and necrosis with acute exposures > or = 10 mg/m3. Lung instillations at 250, 500, and 1000 micrograms of the VDM revealed no lung or liver toxicity. Because per os exposure due to preening was suspected as a major exposure route, a gavage study with the VDM and its two component dyes DR11 and DB3 (800 mg/kg) was undertaken. One day following gavage with DR11 or DB3, serum enzymes indicative of liver toxicity (LDH, SGPT, SDH, and ICDH) were slightly elevated (1-6x control). However, rats gavaged with VDM had serum enzyme levels 10-100x control by Day 1 after gavage, indicating acute liver toxicity. Activities of liver enzymes involved in xenobiotic and glutathione metabolism were also acutely affected. All of the dyes caused various degrees of induction of glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, and nonprotein sulfhydryls. The enzymes involved in xenobiotic metabolism (glutathione S-transferase, NADPH cytochrome-c reductase, and P450) were also elevated by the two component dyes, in contrast to their significant depression with VDM treatment. The similarity between the liver and olfactory epithelium effects of these compounds and the lack of pulmonary tissue effects is not fully understood, but the interaction of the individual dyes as VDM emphasizes the need to assess chemicals such as the anthraquinones as their likely-to-be-encountered mixtures.
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PMID:Toxicity of an anthraquinone violet dye mixture following inhalation exposure, intratracheal instillation, or gavage. 812 3

There have been numerous reports of altered drug clearance during episodes of viral infection and during the clinical use of recombinant interferons, but there have been very few reports regarding the effect of active bacterial infections on cytochrome P450-mediated metabolism. The objective of this study was to determine the mechanism by which the Gram-positive bacteria Listeria monocytogenes causes a depression of cytochrome P450-mediated biotransformation in mice. After induction with beta-napthoflavone, hepatic microsomal cytochrome P450 levels were reduced by 40% and ethoxyresorufin-O-dealkylase (EROD) activity was decreased by 65% in mice infected for 48 hr. The loss of EROD activity was accompanied by losses of cytochrome P450IA apoenzyme and cytochrome P450IA mRNA. Listeria infection did not affect total mRNA levels, as determined by oligo(dT)18 hybridization. The time course of these effects demonstrated that an up-regulation of cytochrome P450IA preceded the loss of this isozyme and that changes in cytochrome P450IA mRNA preceded the changes in apoenzyme levels and EROD activity. In hepatic microsomes from uninduced mice, cytochrome P450 levels and the rates of dealkylation of ethoxyresorufin, benzyloxyresorufin, pentoxyresorufin, and aminopyrine were significantly reduced, by 40-60%, after 48 hr of infection. The decrease in aminopyrine-N-demethylase activity was accompanied by a loss of cytochrome P450IID9 mRNA after 48 hr of infection. Cytochrome P450IID9 mRNA levels returned to normal after 96 hr of infection, whereas aminopyrine-N-demethylase activity was still decreased at this time. No up-regulation of cytochrome P450IID9 occured before the loss of this isozyme. The results of this study indicate that the changes in the levels of cytochrome P450IA and cytochrome P450IID9 that are observed during L. monocytogenes infection occur at a pretranslational step. If other bacteria have a similar capacity to depress cytochrome P450 by such a mechanism, then drugs with narrow therapeutic indices should be administered with caution during infectious diseases caused by bacteria or viruses.
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PMID:Mechanism of hepatic cytochrome P450 modulation during Listeria monocytogenes infection in mice. 837 89

The activity of four recombinant human cytokines on porcine neutrophils was evaluated. Porcine neutrophils were treated with varying doses of recombinant human tumour necrosis factor-alpha (rHu-TNF), interferon-gamma (rHu-IFN), interleukin-8 (rHu-lL-8), or granulocyte-macrophage colony-stimulating factor (rHu-GM-CSF). The function of treated neutrophils was compared with that of non-treated controls in the following assays: antibody-independent neutrophil cytotoxicity (AINC), antibody-dependent cell-mediated cytotoxicity (ADCC), iodination, Staphylococcus aureus ingestion, cytochrome C reduction, random migration, and chemotaxis. Treatment with rHu-TNF produced significant (P < 0.05) depression of neutrophil random migration (2.5, 25, and 250 ng ml-1 rHu-TNF) and iodination (250 ng ml-1) and a near significant (P = 0.08) depression in ADCC (250 ng ml-1). Treatment with 25,000 U ml-1 of rHu-IFN caused a significant increase in AINC. At lower doses of rHu-IFN, there was a trend (0.05 < P < or = 0.08) toward depression of AINC (250 U ml-1) and ADCC (25 U ml-1) and enhancement of iodination (250 U ml-1). Treatment with 50 ng ml-1 of rHu-IL-8 caused a near significant increase (P = 0.06) in AINC. There were no significant differences noted when porcine neutrophils were treated with rHu-GM-CSF (2.5-2500 U ml-1). No synergism was noted between rHu-TNF and rHu-IFN.
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PMID:Effect of recombinant human cytokines on porcine neutrophil function. 839 2

Fluoxetine and other selective serotonin reuptake inhibitors (SSRIs) are effective for the treatment of depression in the elderly and offer a safer side-effect profile as compared to tricyclics and monoamine oxidase inhibitors. We report a case in which a patient treated with fluoxetine developed parkinsonism following the introduction of cimetidine. Inhibition of hepatic P450 cytochrome enzymes by cimetidine with an increase in serum levels of norfluoxetine may have precipitated this extrapyramidal syndrome, which has been related to agonism of the serotonergic input to nigrostriatal tracts and basal ganglia. Parkinsonism as a side effect of SSRIs occurs infrequently, suggesting an idiosyncratic response resulting from a functional imbalance of serotonergic and dopaminergic activity in susceptible individuals. Careful monitoring of geriatric patients treated with fluoxetine is indicated, particularly for those on high doses, those with impaired hepatic functioning, or those treated with concurrent medications that slow the metabolism of fluoxetine.
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PMID:Parkinsonism associated with fluoxetine and cimetidine: a case report. 856 37

The expression of constitutive and inducible cytochrome P450s has been shown to be downregulated by interferon through an unknown pretranslational mechanism that depresses the mRNA encoding P450 apoproteins. To establish an association between gene transcription and P450 apoprotein downregulation by interferon, we studied the effect of recombinant interferon (IFN-alpha 2a) on CYP1A1 in human B lymphoblastoid cell lines. The cHoI cell line expresses inducible native CYP1A1, while the genetically engineered derivative h1A1 v2 expresses a noninducible extrachromosomal vector-derived human CYP1A1 cDNA lacking the CYP1A1 promoter region. We characterized CYP1A1 activity, apoprotein, and mRNA by ethoxyresorufin O-deethylase activity, Western immunoblotting, and Northern blot analysis, respectively. In cHoI cells, following induction with dibenz[a,h]anthracene, interferon depressed CYP1A1 apoprotein and mRNA levels by 55 and 76%, respectively, with no detectable changes in enzyme activity. In h1A1 v2, however, interferon increased CYP1A1 activity, apoprotein, and mRNA. The depression of CYP1A1 mRNA and apoprotein levels incHoI cells, in contrast with the increase observed in h1A1 v2 cells, suggests that nuclear mechanisms are essential for interferon-mediated depression of inducible P450s. From our preliminary results we propose that interferon-mediated downregulation of CYP1A1 may result from inhibition of gene transcription.
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PMID:Interferon-mediated changes in the expression of CYP1A1 in human B lymphoblastoid (AHH-1 TK +/-) cells. 883 82

46 patients with infectious-and-allergic myocarditis (IAM) and 46 patients with myocarditic cardiosclerosis (MCS) were studied for cytochemical parameters of blood lymphocyte bioenergetics. In IAM, cellular metabolism was found out to be disturbed, with the activity of G-6-PDG in spontaneous NST-test being risen against the background of depression of NAD- and NADP-diaphorases, lowering of the endogenous cytochrome "C" content and activity of alpha-GPDG. One third of IAM patients demonstrated protracted variant of the disease course by a study into the bioenergetic status of blood lymphocytes. Examination of parameters of blood lymphocytes energy exchange permits establishing more differential and diagnostic criteria for inflammatory lesion of the myocardium.
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PMID:[The bioenergetics system of the blood lymphocytes in infectious-allergic myocarditis]. 907 68


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