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 process(es) by which parenteral iron effects the accumulation of hepatic metallothionein (MT) is not known. The present study examined glucocorticoids as potential mediators of this process. Chicks were given either one injection (ip) of iron (+1FE) at 10 mg Fe/kg, two injections of iron (+2FE) given 24 hr apart, or a single injection of saline. Plasma corticosterone was evaluated at various times following the last injection. Plasma corticosterone increased approximately 50% following +1FE but more than 200% at 2 and 4 hr following a second injection of iron (+2FE). Plasma zinc showed a transient increase followed by a considerable depression. Coincidentally, the accumulation (determined at 24 hr) of zinc MT in liver of +2FE chicks was three times higher than that of +1FE chicks. In another experiment, markedly greater changes, at similar time intervals, in plasma corticosterone were effected by multiple subcutaneous injections of adrenocorticotropic hormone (ACTH) (either 5 IU ACTH or 20 IU ACTH/kg). Subsequent analysis of hepatic zinc MT showed only minor changes as a result of ACTH injections. These results indicate that a change in the plasma glucocorticoid corticosterone is not a primary component in the process(es) by which parenteral iron effects an increase in hepatic zinc MT.
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PMID:Iron-induced accumulation of hepatic metallothionein: the lack of glucocorticoid involvement. 303 18

Experiments were conducted to examine the role of zinc in the prevention of bromobenzene hepatoxicity in male rats. Bromobenzene (BB) (7.5 mmol/kg, ip) produced a marked hepatotoxicity as evidenced by increases in plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and a marked depression in hepatic glutathione (GSH) content 24 hr after administration. The administration of zinc (92 mumol Zn/kg, ip, at 48 and 24 hr prior to the bromobenzene) ameliorated the bromobenzene elevations in plasma AST (25%) and plasma ALT (50%) but did not alter the decreases in hepatic GSH. Following administration of [14C]BB, the radioactive label was distributed primarily in the cytosolic and lipid fractions derived from liver homogenates. Furthermore, the subcellular distribution of [14C]BB was not altered by zinc pretreatment. The extent of covalent binding of [14C]BB metabolites to hepatic tissue was significantly depressed in zinc-treated rats. Zinc induced the hepatic levels of metallothionein but [14C]BB did not bind to this sulfhydryl rich protein. Further experiments showed that zinc treatment depressed cytochrome P-450 content, the activity of NADPH cytochrome c reductase, and the metabolism of aniline, but not that of ethylmorphine. These studies suggest that the hepatoprotective effect of zinc against bromobenzene toxicity does not involve altered binding of the reactive toxic metabolite to glutathione or metallothionein, but it may be mediated by the inhibitory effect of zinc on the microsomal cytochrome P-450-dependent drug metabolizing system.
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PMID:Amelioration of bromobenzene hepatotoxicity in the male rat by zinc. 398

Male ICR mice were either given water containing Cd at a level of 192-200 ppm for 45 days (ingestion group), or were injected subcutaneously once a week with Cd (1 mg/kg) as CdCl2 for 7 weeks (injection group). The control group was given Cd-free water. In both Cd groups, the hematocrit and hemoglobin values did not change markedly. In the ingestion group, the Fe concentration decreased greatly in the liver, kidney, spleen, and duodenum. These decreases may be due to depression of Fe absorption from the intestine. In the injection group, Fe increased in the liver, spleen, and duodenum, although it decreased in the kidney. By Sephadex G-200 gel filtration, Fe-proteins in the hepatic supernatants were located in the void volume region of this gel column in both Cd groups. Apparently, Fe was not a component of metallothionein (MT) protein. The hepatic MT induction by Cd resulted in an increase in hepatic supernatant Cu. Serum Cu and ceruloplasmin (Cp) activity were stimulated only in the injection group. The enhancement of Cp activity may possibly be due to the increase in hepatic Cu which was accompanied by an increase in hepatic Fe, rather than a decrease. Our observations suggest that Fe metabolism is influenced differentially by the administration route of Cd.
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PMID:Effects of subcutaneous and oral cadmium on iron metabolism: role of ceruloplasmin and metallothionein. 651 7

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 concentration of metallothionein (MT) in the liver of the perinatal rat is relatively high at term and 7 days after birth and then decreases to barely detectable levels by day 28. The developmental pattern MT-zinc parallels that of MT. When challenged with a single injection of cadmium chloride, the 26-day-old rat responds with a dose-related increase in hepatic MT which sequesters both cadmium and zinc. When the 5-day-old rat is similarly challenged, induction of MT occurs only at the highest dose tested (6 mg Cd/kg); however, due to the pre-existence of MT in these younger rats, cadmium administered at the lower doses still binds to the MT in a dose-related manner. Despite the induction of MT seen in both age groups following the 6.0 mg/kg dose, exposure to that level of the metal produced death in 30% of the younger animals but in only 4% of the older animals. When cadmium was administered to pregnant rats on day 19 of gestation, it was found to produce a dose-related induction of maternal hepatic MT over the following 48 hr. In contrast, maternal exposure to the metal led to a significant depression of fetal hepatic MT over the same time interval.
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PMID:Role of hepatic metallothionein during perinatal development in the rat. 705 77

Pregnant rats were injected subcutaneously on day 10 of pregnancy with 0.0, 0.25, 0.50, 1.0 or 3.0 mg cadmium/kg and sacrificed at term (day 21). There were no fetal or maternal deaths following the cadmium exposure with the exception of the e.0 mg/kg level where a 54% fetal mortality rate was observed. At doses of 1.0 mg/kg or less, non-specific parameters of fetal toxicity including body weight, crown-rump length, and liver weight were not significantly different from control values. The same was true of term placental weight as well as maternal weight gain over the 48-h treatment period. Following gel-filtration of hepatic cytosols from control fetuses, over 70% of the endogenous cytosolic zinc was associated with a peak previously described as metallothionein. It was found that cadmium exposure at sub-lethal doses caused a depression in both total cytosolic zinc and metallothionein-bound zinc levels in the fetus, whereas both these parameters increased in the maternal liver. In vitro cadmium saturation prior to gel filtration revealed that the cadmium-binding capacity of the metallothionein peak was significantly reduced at all dosage levels in the fetus but increased in maternal liver. These findings suggest that maternal administration of cadmium can depress fetal metallothionein levels and cytosolic zinc levels at doses which do not produce overt fetal toxicity. This reduction in fetal metallothionein is in sharp contrast with the well established finding of induction of metallothionein seen in the adult following exposure to cadmium.
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PMID:Depression of metallothionein in fetal rat liver following maternal cadmium exposure. 725 78

The effects of sublethal waterborne Zn2+ (150 micrograms l-1 = 2.3 mumol-1) on the kinetics of unidirectional Ca2+ influx were studied in juvenile freshwater rainbow trout during chronic exposure (60 days) at a water [Ca2+] of 1.0 mmol l-1. An unexposed group held under identical conditions served as control. The presence of Zn2+ in the water increased the apparent Km for Ca2+ influx by up to 300% with only a small inhibitory effect (35% at most) on the maximum rate of uptake (Jmax). These results, in combination with earlier data showing that Ca2+ competitively inhibits Zn2+ uptake, suggest that Zn2+ and Ca2+ compete for the same uptake sites. Acute withdrawal of Zn2+ after 3h of exposure resulted in a 23-fold reduction in Km for Ca2+, but a persistent small depression of Jmax. During prolonged exposure to Zn2+, the apparent Km for Ca2+ remained greatly elevated and Jmax remained slightly depressed. The actual Ca2+ influx in hard water ([Ca2+] = 1.0 mmol l-1) decreased marginally and paralleled the small changes in Jmax. The increases in apparent Km had a negligible influence on the actual Ca2+ influx because Km values (38-230 mumol l-1), even when elevated by Zn2+, remained below the water [Ca2+] (1000 mumol l-1). Rainbow trout exposed to Zn2+ exhibited a slower rate of protein synthesis in the gills (measured on day 23) and an increased tolerance to Zn2+ challenge (measured on both days 27 and 50). Unidirectional Zn2+ influx, measured at the end of the exposure period, was significantly reduced in the Zn2+-exposed fish. There were no changes in hepatic or branchial Zn2+, Cu2+ or metallothionein concentrations. We hypothesize that, during exposure to sublethal [Zn2+] in hard water, the fish may change the Km for a mutual Ca2+/Zn2+ carrier so as to reduce markedly Zn2+ influx without greatly altering Ca2+ influx. This reduced Zn2+ influx, rather than metallothionein induction, may be the basis of adaptation to elevated concentrations of waterborne Zn2+.
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PMID:Effects of zinc on the kinetics of branchial calcium uptake in freshwater rainbow trout during adaptation to waterborne zinc. 752 31

Glucocorticoids (GC) have an important effect on mood in humans and influence learned helplessness, an escape avoidance paradigm that is considered one of the best animal models of depression. A strong genetic component underlies the development of learned helplessness as shown by the emergence of a line of highly vulnerable rats (LH strain) through selective inbreeding. In addition, hormonal factors play a role. Adrenalectomy (adx) for example is known to increase the vulnerability to acquire learned helplessness, an effect that is reversed by glucocorticoids (GC). Since GC function primarily by modulating gene expression, hormone mediated alterations in mRNAs expressed in the brain may be important in the development of an adequate escape avoidance response. Conversely, we postulate that the deficit in escape avoidance behavior exhibited by the LH strain may be associated with an alteration in GC-mediated gene expression in the brain. To test this hypothesis, we analyzed GC-responsive mRNAs that are expressed in the hippocampus. Control Sprague-Dawley (SD) rats showed consistent alterations in mRNAs that are modulated by GC, such as type II GC receptor (GR) and metallothionein-1 (MT-1). Under our experimental conditions, both GR and MT-1 mRNA are significantly increased in the hippocampus of hormone-treated SD rats. An increase in hypothalamic GR mRNA was also observed. However, under the same experimental conditions, LH rats showed more selective hormone induced changes since GC had no effect on hypothalamic and hippocampal GR mRNA whereas a significant increase in MT-1 mRNA was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations in glucocorticoid inducible RNAs in the limbic system of learned helpless rats. 768 29

The appearance of joint inflammation (JI) 14 days after the injection of adjuvant (AJ) in the tail of rats is associated with a cachectic syndrome which is characterised by marked weight loss (WL). The degree of weight loss was examined in relation to the extent of change in other markers of inflammation including increased plasma copper (pCu), decreased plasma zinc (pZn) and increased hepatic metallothionein (hMT). At 14 days post-AJ injection, arthritic rats showed the following changes, relative to the controls: body weight, 12% decrease, pZn, 50% decrease; pCu, 90% increase and hMT, 11-fold increase (all p < 0.001). Significant relationships were observed between JI, WL, pZn and hMT. The following coefficients of determination (r2) were observed; JI and WL, -0.530, JI and pZn, -0.485; JI and hMT, 0.286; WL and hMT, -0.510 (all p < 0.007). There was a strong relationship between the decreased pZn and increased hMT; r2 = 0.456 (p < 0.001). While increased pCu was clearly associated with AJ-arthritis in these rats, there was no quantitative relationship between the extent of change in pCu and the other parameters measured (r2 all < 0.01). The highest correlation observed was between pZn and WL (r2 = 0.637, p < 0.001). While the initial depression of pZn may be the result of increased hepatic hMT levels, longer term reductions in pZn levels are linked to systemic inflammation, the degree of arthritis and associated weight loss.
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PMID:Wasting in adjuvant-induced arthritis and its relationship to plasma zinc, copper and liver metallothionein. 784 86

This article is based on data on the levels of metals (Cd, Zn, Cu) and metallothionein (MT) determined radiochemically with 203Hg in renal cortex and liver of 137 autopsy cases. From this number, for 23 cases, the gel filtration of the cytoplasmic fraction of the organs was performed. The molar content of metals in the MT fraction (Sephadex G-50) amounted to 46.9, 50.2, and 2.0% for Cd, Zn, and Cu in renal cortex, respectively, and to 8.3, 83.6, and 9.1% for Cd, Zn, and Cu in the liver, respectively. In parallel with the increase of Cd and MT in renal cortex, increasing saturation was found of the MT fraction by Cd, occurring at the expense of Zn and Cu. Equimolar amounts of Cd and Zn in the MT fraction are found at Cd level of 0.5 micromol Cd/g wet wt of renal cortex. In the liver, analogous dependency (elevation of %Zn, depression of %Cd and %Cu) were observed in relation to Zn and MT levels in this organ. The basic level of Zn (not bound with MT) was estimated at 0.5 micromol/g for both renal cortex and liver. A deficit of non-MT Zn in kidneys is proposed as an alternative mechanism of toxic Cd action.
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PMID:Metal composition of human hepatic and renal metallothionein. 988 17


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