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

Effects of doxapram, a respiratory stimulant, on the action of other drugs and the activity of the hepatic drug-metabolizing enzyme were studied in mice. The hypothermic effect induced by aminopyrine and the muscle relaxant effect induced by meprobamate were potentiated by the pretreatment with doxapram 60 min before. Furthermore, doxapram significantly enhanced the lethalities of picrotoxin and strychnine and the analgesic actions of aminopyrine and morphine. The plasma concentration of aminopyrine or pentobarbital in doxapram-treated mice was higher than those in untreated mice, and the plasma concentration of normustard related to an active metabolite of cyclophosphamide after the administration of cyclophosphamide was lower in doxapram-treated mice. On the other hand, doxapram (50 mg/kg, i.p.) reduced remarkably the activities of aminopyrine N-demethylase and aniline hydroxylase in the hepatic 9,000xg supernatant fraction, and also reduced the cytochrome P-450 contents in hepatic microsomes. However, no significant alteration by doxapram was observed on the activities of NADH-ferricyanide reductase and NADPH-cytochrome c reductase and cytochrome b5 contents. It seems likely that the mechanisms of the interaction between doxapram and combined drugs involved the depression of the hepatic drug-metabolizing system in microsomes and a subsequent variation of drug level in the plasma.
 ...
PMID:Effect of doxapram on the action of other drugs and the hepatic drug-metabolizing system in mice. 713 53

Toxins produced by Clostridium difficile are lethal to mice after i.p. administration. Among the alterations observed when mice were given a preparation containing both Toxin A and Toxin B were a 1.6 +/- 0.2 degrees C (mean +/- S.E., N = 7) depression of rectal body temperature, blood in the liver (318 +/- 13% of control levels) and a decrease in glutathione concentration (74 +/- 2% of control). Purified Toxin A and purified Toxin B were both able to alter these parameters. Toxin B, however, had a more profound effect on serum isocitrate dehydrogenase levels (raised to 198 +/- 18% of control) and liver O-demethylase activity (reduced to 64 +/- 8% of control), parameters sensitive to alteration in liver damage. The effects of Toxin B on these parameters were partially alleviated in mice pretreated with N-acetylcysteine (1.2 g/kg i.p.) and triamcinolone (120 mg/kg i.p.) and, although the percentage of survivors did not improve, survival time was increased from 3.0 +/- 0.1 hr to 4.6 +/- 0.5 and 5.7 +/- 1.3 hr, respectively, by these agents.
 ...
PMID:Biochemical and pathological effects of Clostridium difficile toxins in mice. 716 14

Male ICR mice (25 - 30 g) were pretreated with bovine hematin (20, 40 or 50 mumoles per kg per day, i.p.) for three days. During the next six-day period, animals received either 50 mg per kg per day propoxyphene-HCl or saline, p.o., in addition to the daily hematin injections. Only the highest hematin regimen depressed the induction of propoxyphene-N-demethylase activity significantly in the drug-treated animals. A similar depression below control levels was noted in the animals receiving only saline (p.o.) and hematin (i.p.). While hematin treatment abolished the metabolic tolerance to propoxyphene analgesia such treatment failed to generate any appreciable degree of physical dependence to propoxyphene as assessed by a challenge with naloxone. These findings may be helpful in assessing the risk factors associated with the widespread use of propoxyphene.
 ...
PMID:The effect of hematin on the development of microsomal enzyme induction and physical dependence in mice following repeated oral propoxyphene administration. 719 21

Four- to five-week-old male and female Sprague Dawley rats were exposed to vapors of methanol (2500 ppm), gasoline (3200 ppm), and methanol/gasoline (2500/3200 ppm, 570/3200 ppm) six hours per day, five days per week for four weeks. Control animals were exposed to filtered room air only. Depression in body weight gain and reduced food consumption were observed in male rats, and increased relative liver weight was detected in rats of both sexes exposed to gasoline or methanol/gasoline mixtures. Rats of both sexes exposed to methanol/gasoline mixtures had increased relative kidney weight and females exposed to gasoline and methanol/gasoline mixtures had increased kidney weight. Decreased serum glucose and cholesterol were detected in male rats exposed to gasoline and methanol/gasoline mixtures. Decreased hemoglobin was observed in females inhaling vapors of gasoline and methanol/gasoline at 570/3200 ppm. Urine from rats inhaling gasoline or methanol/gasoline mixtures had up to a fourfold increase in hippuric acid, a biomarker of exposure to the toluene constituent of gasoline, and up to a sixfold elevation in ascorbic acid, a noninvasive biomarker of hepatic response. Hepatic mixed-function oxidase (aniline hydroxylase, aminopyrine N-demethylase and ethoxyresorufin O-deethylase) activities and UDP-glucuronosyltransferase activity were elevated in rats exposed to gasoline and methanol/gasoline mixtures. Histopathological changes were confined to very mild changes in the nasal passages and in the uterus, where decreased incidence or absence of mucosal and myometrial eosinophilia was observed in females inhaling gasoline and methanol/gasoline at 570/3200 ppm. It was concluded that gasoline was largely responsible for the adverse effects, the most significant of which included depression in weight gain in the males, increased liver weight and hepatic microsomal enzyme activities in both sexes, and suppression of uterine eosinophilia. No apparent interactive effects between methanol and gasoline were observed.
 ...
PMID:Short-term inhalation toxicity of methanol, gasoline, and methanol/gasoline in the rat. 748 74

Streptolysin O, a thiol-activated exotoxin from group A beta-haemolytic streptococci, caused a dose-dependent depression of aniline hydroxylase, aminopyrine N-demethylase and ethylmorphine N-demethylase activities when added into the hepatic microsomal mixtures from male rats at concentrations 0.02-0.4 HU/mL in vitro. The activities of 7-ethoxycoumarin O-deethylase, 7-ethylresorufin O-deethylase and 7-pentylresorufin O-depentylase were not altered with the used concentrations of the toxin. Specific antibody against haemolytic action of streptolysin O added to incubation mixtures in vitro was not able to protect streptolysin-sensitive monooxygenases from the inhibition. The addition of streptolysin O (0.01-0.8 HU/mL) into the cytosol-containing medium did not significantly influence the activity of procainamide N-acetyltransferase. Immunomodulators picibanil (OK 432) and human recombinant interferon alpha 2A which are known to suppress oxidative metabolism in vivo in humans and animals, were without effect either on the cytochrome P-450-dependent monooxygenases or on the N-acetyltransferase activity when administered in vitro at the doses real in their clinical application (0.001-0.1 KE/mL of picibanil and 10-500 U/mL of alpha-interferon).
 ...
PMID:Effects of streptolysin O, picibanil (OK 432) and interferon alpha 2A on cytochrome P-450-dependent monooxygenases and arylamine N-acetyltransferase in rat liver. 765 Feb 91

The level of 8-OH-2-deoxyguanosine in rat liver DNA was measured as an index of oxidative damage after treating rats for 10 days at a dose ranging from 0.75 to 10 mg/kg with a mixture of 15 pesticides (dithiocarbamate, benomyl, thiabendazole, diphenylamine, chlorthalonil, procimidone, methidathion, chlorpyrifos-ethyl, fenarimol, parathion-methyl, chlorpropham, parathion, vinclozolin, chlorfenvinphos, pirimiphos-ethyl) commonly found in foods of central Italy. At the doses of 0.75 and 1 mg/kg DNA levels of 8-OH-2-deoxyguanosine were significantly increased relative to controls, whereas at higher doses (2.5, 5, 10 mg/kg) the levels returned to control values. The administration of the pesticide mixture dose dependently reduced benzo(a)pyrene hydroxylase, N-demethylase activities, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and thiol transferase activities in the liver. The results show that the pesticide mixture induced free radical DNA damage at low doses. However, at higher doses it produced a depression of cellular metabolism, inhibiting a further expression of oxidative damage.
 ...
PMID:Effect of a mixture of 15 commonly used pesticides on DNA levels of 8-hydroxy-2-deoxyguanosine and xenobiotic metabolizing enzymes in rat liver. 772 83

Male Fischer rats were maintained for a period of 17 weeks on an iron-deficient diet along with suitable controls. The effect of long term deprivation of iron on xenobiotic metabolism was studied by the activities of various drug metabolising enzymes in both liver as well as extra-hepatic tissues like lungs, kidneys and intestinal mucosa (I.M.). The results show that among the Phase I (activating) enzymes, the hepatic activities of benzo(a)pyrene hydroxylase (AHH) and microsomal epoxide hydrolase (mEH) are significantly reduced in iron deficiency. The other parameters of the activating system, namely cytochrome P450, aminopyrene demethylase (ADM) and aniline hydroxylase (AH), are not altered. Of the two Phase II (conjugating) enzymes studied, only uridine diphospho glucuronyl transferase (UDPGT) is found to be depressed, but not glutathione S-transferase (GST) in liver in iron deficiency. Activities of Phase I enzymes are markedly lowered in extra-hepatic tissues compared to liver; such depression is not observed in conjugating enzymes. Iron deficiency does not seem to make much impact on the enzyme activities of extra-hepatic tissues. Overall, the hepatic results suggest a defect in detoxification mechanisms in iron deficiency. Such impairment may very well predispose an iron-deficient host to an increased risk of carcinogenesis.
 ...
PMID:Effect of long term iron deficiency on the activities of hepatic and extra-hepatic drug metabolising enzymes in Fischer rats. 785 40

Aflatoxins are suspected human carcinogens and are also known to possess diverse toxicological activities. In the present communication an attempt has been made to evaluate the effects of aflatoxin B1 (AFB1) on hepatic microsomal drug metabolizing enzymes in growing rats. The weanling rats were exposed to 60, 300 or 600 micrograms AFB1/kg body weight, per os, on alternate days for 4 weeks, in 0.2 ml corn oil. A significant depression in the activities of aryl hydrocarbon hydroxylase (AHH), aniline hydroxylase (AH) and aminopyrene-N-demethylase (AND) was observed at 300 micrograms and 600 micrograms doses of AFB1. However, no significant change was recorded in glutathione-S-transferase (GST) activity and total sulphydryl (SH) content upon AFB1 exposure in weanling rats. Thus, AFB1 appears to have more pronounced effect on the phase I, rather than phase II, biotransformation enzyme system in weanling rats. The depression of drug metabolizing enzymes together with suppression of immunity by AFB1, as reported earlier by us, may increase the susceptibility of the host to toxic chemicals, drugs and infectious agents, particularly during the post-natal period.
 ...
PMID:Aflatoxin induces depletion of activities of phase I biotransformation enzymes in growing rats. 800 97

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.
 ...
PMID:Mechanism of hepatic cytochrome P450 modulation during Listeria monocytogenes infection in mice. 837 89

The antimetastatic effect of GIV-A (fucoidan) and/or 5-FU was examined in an experimental model of lung metastases induced by Lewis lung carcinoma in mice. Injection of GIV-A i.p. after removal of the implanted primary tumor inhibited the development of lung metastases. Combination treatment with GIV-A and 5-FU inhibited significantly the lung metastases. The number of peritoneal macrophages, total cells and macrophages in the lung increased in mice treated with GIV-A. Binding of the third component of complement (C3) cleavage products (C3b) to the C3 receptor on peritoneal macrophages after i.v. injection of GIV-A was enhanced, as shown by the fluorescent antibody technique. Lung metastases were inhibited by i.v. injection of peritoneal macrophages activated with GIV-A. GIV-A depressed aniline hydroxylase and aminopyrine demethylase activities of the hepatic microsomal drug-metabolizing system in tumor-bearing mice. Moreover, the concentration of 5-FU in the tissues (lung, liver, kidney, spleen and blood) was increased significantly by coadministration of GIV-A. The picryl chloride-induced delayed type hypersensitivity (PC-DTH) response in mice was depressed after the implantation of tumor and treatment with 5-FU. GIV-A restored the suppression of PC-DTH by 5-FU, but did not increase the PC-DTH of normal mice. GIV-A not only enhanced the degree of spleen cell-mediated sheep red blood cell (SRBC) hemolysis (quantitative hemolysis of SRBC), the indexes of the spleen and thymus and the number of spleen cells, but also restored the suppressive effect of 5-FU. In the group receiving GIV-A, the percentages of splenic Thy1.2-, L3T4- and asialo GM1-positive cells were significantly increased as compared with the tumor-bearing mice treated with saline. Furthermore, the L3T4+/Lyt2+ ratio showed a tendency to increase, and the Lyt2+/Thy1.2+ ratio was decreased. These results suggest that the antitumor effect of GIV-A may be correlated with the changing pattern of the Thy1.2-, L3T4- and asialo GM1-positive cells, C3 activation, macrophage activation and depression of the hepatic microsomal drug-metabolizing system. These findings raise the possibility that GIV-A may have clinical value in the prevention of cancer metastasis.
 ...
PMID:Immunological analysis of inhibition of lung metastases by fucoidan (GIV-A) prepared from brown seaweed Sargassum thunbergii. 857 81


<< Previous 1 2 3 4 5 6 7 Next >>