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)

The effects of dithiocarb and (+)-catechin on the microsomal mixed-function oxidase system of rat liver were investigated after a single dose as well as after repeated treatment for 7 and for 28 days. Dithiocarb (200 mg/kg p.o.) significantly reduced the microsomal cytochrome P-450 content, aniline hydroxylase and aminopyrine demethylase activities; maximum decrease was observed at 4 hrs, return to normal values after 24 hrs. (+)-catechin (200 mg/kg p.o.) had no effects in this respect. Both agents did not affect microsomal enzyme activities when applied orally for 7 days. After 28 days treatment only dithiocarb (50 - 100 - 200 mg/kg p.o.) exerted a dose-dependent depression of the aniline hydroxylase activity. In vitro experiments confirmed the in vivo observations: a concentration-dependent inhibition of the aniline hydroxylation and aminopyrine demethylation were seen from the addition of dithiocarb, the I50-values were 5.4 X 10(-6) M and 9.6 X 10(-5) M, respectively. (+)-catechin showed no inhibitory activity on both enzyme activities in vitro. Both dithiocarb and (+)-catechin depressed the activity of the NADPH-cytochrome C-reductase only in the 10(-4) M concentration range, these effects should be therefore evaluated as non-physiological without relevance in vivo.
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PMID:Effects of dithiocarb and (+)-catechin on microsomal enzyme activities of rat liver. 628 65

CCl4 administration to rabbits leads to early destruction of liver microsomal cytochrome P-450, to depression of glucose 6 phosphatase, to ultrastructurally revealable alterations and to an intense necrosis and fat accumulation in liver. Despite the known resistance of rabbit liver microsomes to lipid peroxidation, CCl4 administration to rabbits promoted lipid peroxidation of their liver microsomal lipids as revealable by the diene hyperconjugation technique, at periods of time from 1 to 12 h. Nevertheless, the intensity of this process is not equivalent to that occurring in rat liver microsomes, since the arachidonic acid content of rabbit liver microsomal lipids does not decrease at either 6 or 24 h after CCl4 administration. Rabbit liver is able to activate CCl4 to reactive metabolites that bind covalently to lipids. Relevance of covalent binding of CCl4 reactive metabolites and CCl4-promoted lipid peroxidation to CCl4-induced rabbit liver injury is analysed.
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PMID:Carbon tetrachloride-induced liver injury in the rabbit. 630 7

In vivo induction of gamma interferon (IFN-gamma) by sensitization of mice with Mycobacterium bovis strain BCG and subsequent challenge with tuberculin depressed the ability of liver homogenates from treated animals to metabolically activate promutagens. The Ames Salmonella typhimurium revertant assay was used for analyses of metabolic conversion of promutagens by liver homogenates. Relative to the mutant frequencies determined with control liver homogenates, induction of IFN-gamma depressed the abilities of homogenates from treated animals to activate N-acetylaminofluorene (AAF), aflatoxin B1 (AFB1), and benzo[a]pyrene (BP) by 55%, 44% and 95%, respectively. Within 18-24 h of Aroclor 1254 treatment, liver P-450 content had increased 43%, and the relative mutant yields per unit protein for all three promutagens had approximately doubled. In vivo induction of IFN-gamma suppressed the Aroclor 1254-dependent increases in mutagenesis by AAF (63%), AFB1 (90%), and BP (reduced to a level 23% below non-Aroclor 1254 treatment). In all cases, the levels of depression of promutagen activation qualitatively correlated with cytochrome P-450 content and the induction of IFN-gamma.
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PMID:Gamma interferon induction depresses murine hepatic promutagen/procarcinogen activation. 641 4

Eleven patients with moderate drug-induced liver changes were found to have extremely low hepatic vitamin A levels (less than 10% of normal). Their serum vitamin A, retinol-binding protein, and transthyretin were only slightly affected. In rats, two representative drugs (phenobarbital and methylcholanthrene) produced a significant depression of hepatic vitamin A, whereas plasma vitamin A levels remained normal. The livers of drug-treated animals showed no abnormalities except for the expected proliferation of the smooth endoplasmic reticulum and induction of microsomal enzymes and cytochrome P-450 (phenobarbital) and P-448 (methylcholanthrene). These findings suggest that the decrease in hepatic vitamin A may be secondary, at least in part, to enhanced microsomal metabolism.
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PMID:Decreased hepatic vitamin A after drug administration in men and in rats. 650 38

Interferon inducers, poly I:poly C, endotoxin, hepatic RNA, and Tilorone, were administered to rats at different time points in relation to the onset of hyperoxic exposure (O2 greater than 97%). All interferon inducers tested significantly reduced the mortality of rats when compared with the control groups. In hyperoxia alone, malondialdehyde, a product of lipid peroxidation, was significantly increased and the microsomal enzyme NADPH cytochrome c reductase decreased as measured in the whole lung. With the administration of either endotoxin or poly I:poly C these two parameters remained within the range of control values. These data suggest that the administration of interferon inducers protects against hyperoxic microsomal damage. After the administration of these interferon inducers with or without hyperoxia the increased activity of heme oxygenase and marked reduction of the heme content of microsomes were demonstrated. Since cytochrome P-450 and b5 are the major hemoproteins of microsomes and the known source of oxygen-free radical generation, the results obtained in this study appear to indicate that the depression of the hemoprotein of microsomes by the administration of interferon inducers may be largely responsible for the protective effects of these agents against hyperoxia.
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PMID:Protective effect of interferon inducers against hyperoxic pulmonary damage. 654 2

Exposure of rats to 0.1 and 0.5 mg Cd/kg subcutaneously (s.c.) thrice weekly for 5 weeks resulted in an accumulation of cadmium in the liver in concentrations of 40 and 95 micrograms/g tissue, respectively, and a microsomal burden of Cd amounting to approx. 2-3% of the retained cadmium. The cytoplasm contained about 80% of the cadmium. At an exposure dose of 0.1 mg Cd/kg, stimulation of lipid peroxidation by 22% and inhibition of ALA synthetase by 16% in the liver were observed. The higher exposure of 0.5 mg Cd/kg caused an inhibition of microsomal monooxygenase with depression of cytochrome P-450 and cytochrome b5 by 20% (over 2-fold prolongation of hexobarbital sleeping time and statistically significant decrease of activity of aniline p-hydroxylase). The loss of cytochrome P-450 probably was due to an intensified lipid peroxidation and induction of heme oxygenase (30% and 60% over control, respectively). Sequestration of cadmium by cytoplasm (metallothionein) does not protect microsomes against cadmium accumulation and specific biochemical disturbances.
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PMID:Stimulation of lipid peroxidation and heme oxygenase activity with inhibition of cytochrome P-450 monooxygenase in the liver of rats repeatedly exposed to cadmium. 654 50

The heme-cytochrome P-450 complexes represent sensitive metabolic systems for examining the biological impact of metals on important cellular functions. Many metals, both in the inorganic form and bound to organic moieties, potently induce heme oxygenase, the rate limiting enzyme of heme degradation. The resulting increase in the rate of heme breakdown is reflected in a marked depression of cellular cytochrome P-450 content and impairment of the oxidative metabolism of natural and foreign chemicals dependent on this hemeprotein. Organometal complexes do not mimic in all their aspects the actions of the inorganic elements which they contain. For example, organotins, in contrast to inorganic tin, produce a prolonged induction response of heme oxygenase in the liver but not in the kidney. Co-protoporphyrin is a much more potent inducer of heme oxygenase in liver than is inorganic cobalt; and Sn-protoporphyrin inhibits heme oxygenase activity nearly completely, whereas inorganic tin is a powerful inducer of the renal enzyme. Contrasting effects on heme metabolism exist as well within the metalloporphyrin species as demonstrated by the effects in vivo of Co-protoporphyrin and Sn-protoporphyrin on heme oxygenase activity; the former induces the enzyme whereas the latter potently inhibits it. In vitro, however, both compounds competitively inhibit heme oxidation activity. These differences, among others which characterize metal actions in vivo and in vitro attest to the importance of pharmacokinetic, adaptive and other host factors in defining the responses of the heme-cytochrome P-450 systems to the impact of metals in the whole animal.
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PMID:Control of heme and cytochrome P-450 metabolism by inorganic metals, organometals and synthetic metalloporphyrins. 654 1

The prior administration of reduced glutathione (GSH) partially prevents carbon tetrachloride (CCl4)-induced liver necrosis observed at 24 h after administration of the hepatotoxin. No prevention occurs when observations are made at 72 h. GSH pretreatment does not significantly modify the intensity of the covalent binding of CCl4 reactive metabolites to microsomal lipids or the intensity of the CCl4-induced lipid peroxidation process at either 1, 3 or 6 h after poisoning. GSH administration does not significantly prevent CCl4-induced cytochrome P-450 destruction or glucose 6 phosphatase activity depression. Pretreatment with GSH does not significantly modify the levels of CCl4 or i.p. administered CCl4 reaching the liver at 1, 3 or 6 h after intoxication. Pretreatment with GSH significantly prevents CCl4-induced decreases in body temperature. Results are interpreted as suggesting that GSH prevents CCl4-induced liver necrosis by changing the liver cell's response to injury rather than by modification of early events of the process such as lipid peroxidation or covalent binding of reactive metabolites.
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PMID:Studies on the mechanism of glutathione prevention of carbon tetrachloride-induced liver injury. 661 8

Pretreatment of rats with ethanol extract from leaves of Aucuba japonica (600 mg/kg/day, po) for two days protected against CCl4-induced depression in plasma disappearance and biliary excretion of injected sulfobromophthalein (BSP) determined 24 hr after the CCl4 challenge (0.5 ml/kg, ip). Percent recovery of BSP in bile in 60 min for control, CCl4, extract + CCl4 treated rats was 66.8 +/- 1.9, 56.2 +/- 1.4, and 68.9 +/- 2.2, respectively. Pretreatment of the extract also protected CCl4-induced increased serum glutamic-pyruvic transaminase activity and liver necrosis as demonstrated by histological evaluations. However, pretreatment of the extract did not modify the intensity of CCl4-induced lipid peroxidation process or cytochrome P-450 destruction. The results suggest that ethanol extract of Aucuba japonica protects CCl4 hepatotoxicity at a site in the chain events leading to necrosis but not the activation step of CCl4 to X CCl3 and X C1 free radicals.
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PMID:Protective effect of Aucuba japonica against carbon tetrachloride-induced liver damage in rats. 662 65

Several 5-halopyrimidinones have been shown to have many different biological activities. These include interferon induction, antitumor effects, modulation of immune responses, and polyclonal B-cell activation. The present study was carried out to determine the effects of treatment of mice with two 5-halopyrimidinones, 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP) and 2-amino-5-iodo-6-phenyl-4(3H)-pyrimidinone (AIPP), on the murine cytochrome P-450 system. Administration of ABPP or AIPP to mice by a dosage regimen similar to that resulting in interferon induction by these chemicals resulted in a significant depression in liver cytochrome P-450 levels. These results suggest that 5-halopyrimidinones can depress cytochrome P-450 levels and that this depression may affect the metabolism of other drugs by cytochrome P-450.
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PMID:Effects of 5-halopyrimidinones with antiviral and antineoplastic activity on murine cytochrome P-450. 670 96


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