Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monooxygenase enzymes are involved in the biotransformation of drugs and of environmental carcinogens. The activity of 7-ethoxycoumarin 0-deethylase and associated NADPH-cytochrome c reductase was determined in 9000 g supernatant from bioptically obtained liver specimens from patients with various liver diseases in order to study in vitro drug metabolising capacity. Monooxygenase and reductase activity was significantly higher in the livers of 21 patients with alcoholic liver disease (fatty liver, alcoholic hepatitis, cirrhosis of the liver) than in 22 normal controls or in six patients with chronic active hepatitis. The raised activity of drug-metabolising enzymes obtained from alcoholics with liver damage differs from normal values found in five alcoholics without liver disease. Both groups were comparable in respect to the amount of alcohol consumed and duration of abuse. A strikingly low monooxygenase activity was observed in eight patients with cirrhosis of the liver and ascites, with, however, no apparent effect on reductase activity. The results show that alcoholic liver disease is associated with enhanced monooxygenase and reductase activity, but alcoholism, per se, is not. This rise of drug-metabolising enzyme activity could lead to selectively increased rates of biotransformation in patients with alcoholic liver damage.
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PMID:Monooxygenase enzyme activity in alcoholics with varying degrees of liver damage. 11 58

The following physiopathological mechanisms for the abnormalities of testosterone metabolism observed in cirrhotic patients may be postulated: 1. The decreased testosterone secretion has a primary testicular origin; it seems probable that, as a result of direct toxicity the 17-beta-reductase is inhibited, resulting in decrease of testosterone and an increase of androstenedione. 2. The hypothalamic-pituitary function is nearly normal in cirrhotics. Basal level of LH and FSH are often slightly elevated, indicating a normal reactivity of the pituitary. 3. The conversion of androgens to oestrogens (androstenedione to oestrone) which occurs essentially extrahepatically, is increaed in cirrhosis.
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PMID:Testosterone metabolism in normal males and male cirrhotics. 15 39

To determine whether ethanol per se affects testosterone metabolism, alcohol was administered to normal male volunteers for periods up to four weeks, resulting in an initial dampening of the episodic bursts of testosterone secretion followed by decreases in both the mean plasma concentration and the production rate of testosterone. The volunteers received adequate nutrition and none lost weight during the study, which tended to exclude a nutritional disturbance as the cause of the decreased testosterone levels. The changes in plasma luteinizing hormone suggested both a central (hypothalamus-pituitary) and gonadal effect of alcohol. In addition, alcohol consumption increased the metabolic clearance rate of testosterone in most subjects studied, probably owing to the combined effects of a decreased plasma binding capacity for the androgen and increased hepatic testosterone A-ring reductase activity. These results indicate that alcohol markedly affects testosterone metabolism independently of cirrhosis or nutritional factors.
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PMID:Effect of alcohol (ethanol) administration on sex-hormone metabolism in normal men. 95 74

This study was performed to ascertain whether testosterone metabolism is altered in male rats with portal bypass, and whether such changes could contribute to the reduction in serum testosterone concentration and raised serum estrogen levels that are observed in this situation. The metabolic clearance rate of testosterone was determined by a prime-dose constant-infusion technique in male rats subjected to complete portal vein ligation and in sham-operated controls. Testosterone clearance was similar in rats with portal vein ligation and control rats (9.01 +/- 2.29 and 8.26 +/- 2.83 ml/min, respectively) but the clearance per gram of liver was greater in rats with portal vein ligation than in controls (1.18 +/- 0.18 versus 0.68 +/- 0.24 ml/min.g liver, p less than 0.0001). After 180 min of [3H]testosterone infusion, [3H]estradiol comprised 1.2% of plasma total radioactivity in male controls but was increased to 11% in rats with portal vein ligation (p less than 0.005). Similarly, biliary excretion of [3H]estradiol was eightfold greater in male rats with portal vein ligation compared with controls (p less than 0.001). In control male rats, the major metabolites of testosterone present in bile were 2 alpha-hydroxytestosterone, 16 alpha-hydroxytestosterone, and 7 alpha-hydroxytestosterone. Portal bypass was associated with reduced biliary excretion of 2 alpha-hydroxytestosterone and 16 alpha-hydroxytestosterone to approximately 50% of control, but there was no change in the excretion of 7 alpha-hydroxytestosterone. Conversely, portal bypass was associated with increased formation of dihydrotestosterone, indicating stimulated activity of testosterone 5 alpha-reductase. It is concluded that portal bypass in male rats is associated with altered pathways of testosterone metabolism and, in particular, with increased aromatization of testosterone to estradiol. The site of such estradiol formation has not been determined by this in vivo study. However, selective changes occurred in the regiospecific and stereospecific hydroxylation pathways of testosterone and in 5 alpha-reductase activity after portal bypass in male rats. It is concluded that portal bypass, in the absence of parenchymal liver damage, results in demasculinization and feminization of C19 steroid metabolism in the male rat liver. These metabolic changes could be revelant to the pathogenesis of changes in sexual characteristics in cirrhosis.
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PMID:Hepatic testosterone metabolism in male rats with portal bypass. 339 70

Liver glutathione-peroxidase (L-GSH-Px) and glutathione-reductase (GSSG-Red) activities were measured in supernatants of liver tissues obtained from a total of 36 subjects. Sixteen of these patients had a functionally normal liver (control group), whereas of the remaining 20 patients, 10 were cirrhotic and 10 had a liver disease other than cirrhosis. The mean value of L-GSH-Px of the control group was 33.12 +/- 12.66 U/g protein, a value similar to that found in patients with liver disease. The L-GSH-Px of the control group was positively correlated with the age of the subjects (r = 0.620; p less than 0.02). In contrast, in patients with liver disease an opposite behaviour of the two parameters was noted (r = -0.497; p less than 0.05). L-GSH-Px activity tended to be higher in males than in females, whereas the erythrocyte glutathione-peroxidase (E-GSH-Px) of the same patients was higher in females, albeit not significantly. L-GSH-Px and E-GSH-Px were not correlated either in normal or in liver disease. The mean GSSG-Red of the control group was 40.63 +/- 11.10 U/g protein, which is not different from that of the group of liver patients. GSSG-Red was not correlated with L-GSH-Px or with the age of patients. In two patients with hepatoma, the GSH-Px activity of the cancer tissue was low and the GSSG-Red activity high.
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PMID:Glutathione-peroxidase and glutathione-reductase activities of normal and pathologic human liver: relationship with age. 625 11

In the liver of 12 patients with porphyria cutanea tarda (PCT) the following parameters were measured: protein-content, NADPH-cytochrome c-reductase, 7-ethoxycoumarin-deethylase. The results were compared with the findings of patients with chronic liver disease (chronic hepatitis or cirrhosis) and patients without any liver affection. In addition the in vitro inhibition of 7-ethoxycoumarin-deethylase by metyrapone (phenobarbital induced cytochrome P-450) or naphthoflavone (benzo[a]pyrene induced cytochrome P-448) was estimated. No differences were found between the various groups. It is assumed that the induction of the mixed function monooxygenases is not an essential condition for the development or the persistence of the human porphyria cutanea tarda.
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PMID:[Cytochrome P-450 dependent enzymatic activity in the liver of patients with porphyria cutanea tarda (author's transl)]. 677 32

A. No consistent changes in the urine PGE2 and PGF2 alpha related to sodium excretion could be found in hepatic cirrhosis with and without ascites. B. Intensive renal sodium retention in cirrhosis with ascites (urine Natless than 20 mEq/24 hr) is very often associated with increasing PGF/PGE ratio, whereas absolute urine PGE2 can be found low or normal. The PG shift is possibly due to a stimulation of the PGE2-9-keto-reductase. C. Application of saluretics and spironolactone in cirrhosis with ascites normalizes the PGF/PGE ratio in accordance with increasing sodium excretion. D. PG changes observed cannot be considered as a primary factor accounting for deranged renal sodium handling in cirrhosis. Anomalous PG pattern possibly reflects enchanced intrarenal vascular resistance.
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PMID:Relationship between urinary prostaglandin (PGE2 and PGF2 alpha) and sodium excretion in various stages of chronic liver disease. 736 21

According to a recent hypothesis, venous thrombosis results from the concurrence of several factors. This hypothesis was assessed in patients with portal or hepatic venous thrombosis by simultaneously investigating most of the currently identified prothrombotic disorders, local precipitating factors, and other risk factors such as oral contraceptive use. Patients with a tumorous obstruction and patients with cirrhosis with portal vein thrombosis were excluded. The prothrombotic disorders that were investigated included classical and occult myeloproliferative disorders; antiphospholipid syndrome; protein C; protein S and antithrombin deficiency; factor V Leiden; factor II; and methylene-tetrahydrofolate-reductase gene mutations. We found 1 or several prothrombotic disorders and a local precipitating factor in 26 and 10 of the 36 patients with portal vein thrombosis, respectively; and in 28 and none of the 32 patients with hepatic vein thrombosis, respectively. We found a combination of prothrombotic disorders in 5 and 9 patients with portal and hepatic vein thrombosis, respectively, whereas such a combination is expected in less than 1% of asymptomatic subjects. Of the 10 patients with a local precipitating factor, 8 had a prothrombotic disorder. Of the 13 patients who use oral contraceptives, 10 had a prothrombotic disorder. We conclude that portal or hepatic venous thrombosis should be regarded as an index for 1 or several prothrombotic disorders, whether or not local precipitating factors or oral contraceptive use are found. Concurrence of prothrombotic disorders is more common than expected. Extensive investigation of prothrombotic disorders and anticoagulation should be considered in patients with portal or hepatic venous thrombosis.
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PMID:Cause of portal or hepatic venous thrombosis in adults: the role of multiple concurrent factors. 1070 47

In clinical trials, all lipid-lowering agents have been associated with mild, asymptomatic elevations of alanine aminotransferase (ALT) and asparate aminotransferase enzymes. This, along with the fact that 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are hepatotoxic in some animals, led the US Food and Drug Administration (FDA) to recommend monitoring of liver enzymes for all lipid-lowering agents, except the bile acid sequestrants. Because the drugs act by different mechanisms, ALT elevations may be a pharmacodynamic effect related to lipid lowering, rather than a direct effect of the drug. Animal studies support this assumption. ALT elevations of 3 times the upper limit of normal occur in <3% of patients in clinical trials of lipid-lowering drugs. The elevations are transient and often dose-related, and they usually revert to normal while continuing therapy and have never been associated with hepatotoxicity. Confounding factors include alcohol, acetaminophen, and pre-existing liver disease, such as chronic hepatitis C and type II diabetes with fatty liver, which are both associated with mild, intermittent elevations of ALT. The more important issue is whether or not lipid-lowering agents are hepatotoxic. There are case reports of hepatotoxicity (cholestasis, jaundice, hepatitis, chronic active hepatitis, fatty liver, cirrhosis and acute liver failure) with all of the drugs, except cholestyramine. To date there are just 5 cases of documented liver failure linked to lovastatin. There is no evidence that monitoring reduces the rate of hepatotoxicity. Mild elevations of ALT that occur with many drugs, including HMG-CoA reductase inhibitors, do not predict hepatotoxicity. Liver enzyme elevations appear to be a class characteristic of lipid-lowering agents. Hepatotoxicity is a rare idiosyncratic reaction, occurring only with sustained released nicotinic acid.
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PMID:Defining patient risks from expanded preventive therapies. 1085 89

The changes in retinoid metabolism have been documented in liver cirrhosis. However, the dynamic alterations in levels of this vitamin between circulation and liver during development of the liver cirrhosis are not well understood. The aim of this study was to measure retinoids in the liver and circulation in parallel, during and after development of cirrhosis induced by carbon tetrachloride and thioacetamide. Retinoid levels were measured by HPLC. A decrease in retinaldehyde and total retinol, together with an increase in retinoic acid was evident in liver from both carbon tetrachloride or thioacetamide treated rats within a month after initiation of treatment. Activity of enzymes involved in retinoid metabolism such as retinaldehyde oxidase, retinaldehyde dehydrogenase, and retinaldehyde reductase were decreased in the liver. In parallel, levels of retinol and retinaldehyde in the serum were increased while retinoic acid was decreased. This study indicates that during development of cirrhosis, there is reciprocal transfer of retinoid metabolites between the circulation and the liver.
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PMID:Retinoid metabolism during development of liver cirrhosis. 1624 80


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