Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.16.3.1 (ceruloplasmin)
5,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammation, induced by turpentine (0.1 ml i.m.), protected against carbon tetrachloride (CCl4)-induced hepatotoxicity based on serum activities of sorbitol dehydrogenase. Inflammation was confirmed by elevated serum ceruloplasmin activities, and was associated with high hepatic levels of metallothionein, a zinc protein proposed to protect against CCl4-induced injury. Inflammation suppressed cytochrome P-450 activities, but this was not associated with protection against CCl4-promoted liver microsomal injury as assessed by glucose-6-phosphatase activity loss. Thus, protection against plasma membrane injury did not result primarily from depressed microsomal activation of CCl4. Each effect of inflammation reported here resembled effects of zinc injections. This similarity strengthens the hypothesis that metallothionein protects against CCl4-induced hepatic plasma membrane injury.
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PMID:Inflammation, an inducer of metallothionein, inhibits carbon-tetrachloride-induced hepatotoxicity in rats. 131 82

Copper feeding studies in rats are generally initiated at weaning. This study examined whether a 6-week feeding of low or marginal Cu levels (0.2 or 2.5 ppm) to rats initially weighing 135 g produced deleterious effects. Controls were fed 8 ppm Cu. Liver Cu-Zn superoxide dismutase activities paralleled Cu intake. Plasma ceruloplasmin activities were very low for both low and marginal Cu consumption. Low but not marginal Cu intake caused a low body weight, high plasma cholesterol level, anemia, cardiac hypertrophy, and a high degree of hepatic plasma membrane injury 24 hours after CCl4 injection (150 microL/kg intraperitoneally [IP]). In summary, low and marginal Cu intakes produced low Cu enzyme activities, while low Cu intake produced pathological symptoms and poor resistance to an oxidative stress.
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PMID:Low and marginal copper intake by postweanling rats: effects on copper status and resistance to carbon tetrachloride hepatotoxicity. 140 98

Induction of hepatic metallothionein (MT) synthesis by several nonmetallic compounds and its relationship to an acute-phase response in inflammation were studied in mice. Subcutaneous injections of menadione, paraquat, carbon tetrachloride (CCl4), and several organic solvents caused an increase of hepatic MT concentration. This MT contained only zinc. Menadione and n-hexane caused the greatest accumulation of hepatic MT among these nonmetallic compounds (about 13-fold). The concentration of Zn was significantly decreased in plasma in contrast to liver after an injection of these nonmetallic compounds. When 65ZnCl2 was injected iv after these injections, uptake of 65Zn to the liver was increased. This effect was not observed after treatment with cycloheximide. The association with inflammation of this induction of MT accumulation was examined by determination of acute-phase proteins. The concentration of fibrinogen in the plasma was significantly increased following injection of those nonmetallic compounds which caused marked hepatic MT accumulation. An injection of 1 N NaOH, 1 N HCl, turpentine oil, or endotoxin caused a significant increase in the plasma concentration of fibrinogen and in the hepatic MT concentration. Injections of n-hexane as well as turpentine oil significantly increased hepatic MT concentration and plasma concentration of fibrinogen and ceruloplasmin with time. The concentration of fibrinogen was significantly correlated (r = 0.789) with the concentration of hepatic MT. Neither adrenalectomy nor pretreatment with dexamethasone prevented hepatic MT accumulation caused by these compounds. These results indicate that induction of hepatic MT synthesis by these nonmetallic compounds is associated with an acute-phase response in inflammation and is independent of glucocorticoids.
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PMID:Induction of hepatic metallothionein by nonmetallic compounds associated with acute-phase response in inflammation. 171 62

Carbon tetrachloride injected to white rats during four days in the dose of 2 g/kg drastically activates intensity of free radical lipid oxidation and induces impairment of the antioxidant system inhibition of the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, a decrease of SH-groups and general plasma ceruloplasmin level and total phospholipids in the liver. The greatest changes are observed by the 7th day. A complex use of tocopherol (30 mg/kg) and dimethyl-sulphoxide produce partial or complete normalization of all the above mentioned values. It is concluded that the optimization of the protective action of the antioxidant system requires a complex use of water and liposoluble antioxidants.
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PMID:[Status of the free radical oxidation and antioxidant system in rats with toxic liver damage; effect of tocopherol and dimethylsulfoxide]. 178 66

Previous experiments showed that the presence of high levels of acute phase reactants (APR) enhance CCl4-induced liver fibrosis in the rat. A high correlation was found between the degree of fibrosis and alpha 2-macroglobulin of the rat (alpha 2-macrofetoprotein, alpha M-FP) used for monitoring the acute phase response. This acute phase reaction was provoked by epinephrine just before CCl4 treatment was started. In the present study we analyzed the effect of APR by repeating these experiments and estimating liver neutral collagenase with a synthetic substrate and endogenous collagen as a substrate, and liver prolyl-4-hydroxylase. A strong depression of liver collagenase activity was found in rats with a preceding acute phase reaction contrary to the rats that underwent CCl4 treatment only. A high level of alpha M-FP correlated negatively with collagenase activity. Also in vitro alpha M-FP proved to inhibit collagenase activity. Prolyl-4-hydroxylase was increased in the rats during acute phase reaction and correlated highly and positively with alpha M-FP, haptoglobin, and ceruloplasmin. Thus high levels of APR promote development of CCl4-induced fibrosis, partly by anticollagenase activity and partly because of enhancement of prolyl-4-hydroxylase activity. The latter phenomenon can also be explained by the presence of APR, but this has to be proved.
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PMID:Mechanisms by which acute phase proteins enhance development of liver fibrosis: effects on collagenase and prolyl-4-hydroxylase activity in the rat liver. 242 60

To investigate the hypothesis that copper deficiency in the rat could result in increased susceptibility to CCl4-induced lipid peroxidation caused by decreased free radical defenses, we performed a series of experiments administering CCl4 to copper-deficient and control rats. Peroxidation after CCl4 administration was monitored by measuring the evolution of expired ethane in closed metabolic chambers. Rats were fed one of two copper-deficient diets based on either evaporated milk or powdered milk. Compared with control values, liver copper content, liver superoxide dismutase activity, and plasma ceruloplasmin level were significantly decreased in copper-deficient rats fed either of the diets. Liver glutathione peroxidase activity was also decreased in the copper-deficient rats fed the evaporated milk diet. Ethane evolution was markedly increased in both copper-deficient groups as compared with their controls. Copper deficiency was also found to produce increases in hepatic iron concentrations, but normal rats loaded with iron dextran to increase hepatic iron concentrations into a range similar to that found in the copper-deficient rats did not exhibit increased ethane evolution after CCl4 administration. Copper deficiency in the rat results in increased CCl4-induced lipid peroxidation.
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PMID:Effects of copper deficiency on carbon tetrachloride-induced lipid peroxidation. 380 65

Four subcutaneous administrations of 2 g/kg of tetrachloromethane to albino rats inhibited the hepatic activity of superoxide dismutase, catalase, glutathione peroxidase, reduced the concentrations of tocopherol, retinol, ascorbic acid, glutathiones, decreased the plasma level of ceruloplasmin and the total antioxidative activity of liver tissue. The magnitude of changes in antioxidative parameters depended on the severity of hepatocytic destruction.
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PMID:[Role of the antioxidant system in the pathogenesis of toxic hepatitis]. 875 48

The hepatoprotective, curative and anti-oxidant properties of aqueous extract of Hybanthus enneaspermus (Violaceae) used against CCl4-induced liver damage in rats were investigated in the present study. Liver damage was induced by CCl4 (1 ml/kg i.p.), and silymarin was used as a standard drug to compare hepatoprotective, curative and antioxidant effects of the extract. Rats were treated with aqueous extract of H. enneaspermus at a dose of either 200 or 400 mg/kg after division into pre-treatment (once daily for 14 days before CCl4 intoxication) and post-treatment (2, 6, 24 and 48 h after CCl4 intoxication) groups. Pre-treatment and post-treatment with aqueous extract of H. enneaspermus showed significant hepatoprotection by reducing the aspartate transaminase, alanine transaminase, and alkaline phosphatase enzymatic activities and total bilirubin levels which had been raised by CCl4 administration. Pre- and post-treatment with aqueous extract significantly decreased hepatic lipid peroxidation as well as producing a corresponding increase in tissue total thiols. Post-treatment with aqueous extract improved ceruloplasmin levels. The histopathological examination of rat liver sections treated with aqueous extract confirms the serum biochemical observations. The present study results demonstrate the protective, curative and anti-oxidant effects of H. enneaspermus aqueous extract used against CCl4-induced hepatotoxicity in rats, and suggest a potential therapeutic use of H. enneaspermus as an alternative for patients with acute liver diseases.
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PMID:Hepatoprotective and antioxidant activity of aqueous extract of Hybanthus enneaspermus against CCl4-induced liver injury in rats. 2147 3