Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum activities of gamma glutamyl transpeptidase, alanine and aspartate aminotransferases, and alkaline phosphatase were determined in children on long-term treatment with aminopyrine. Gamma glutamyl transpeptidase activity was increased up to 15 times above the upper normal limit in children, who received aminopyrine for two weeks or longer. Livers of rats treated with aminopyrine (600 mg/kg/day for 18 to 25 days) had an exceedingly increased activity of gamma glutamyl transpeptidase and a slightly elevated microsomal cytochrome P-450 content. Apparently isolated enhancement of serum gamma glutamyl transpeptidase during aminopyrine medication represents a drug-induced increase of microsomal liver enzymes without clinical relevance and without evidence of damage of liver cells.
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PMID:Aminopyrine--an effective modifier of liver and serum gamma glutamyl transpeptidase. 23 64

Effects of antitumor agents on rat liver microsomal drug-metabolizing enzyme activities and thymus lymphocytes were studied in male Wistar rats. High doses of 5-fluorouracil (5-FU) and cyclophosphamide (CP) given parenterally for 6 days caused a partial decrease in whole body weight and the microsomal enzyme content such as cytochrome P-450 and cytochrome b5. Aniline p-hydroxylase and aminopyrine N-demethylase activities also decreased in rats dosed for 5 days decreased compared with the control. Both compounds in the high concentrations produced spectral change of "modified type II". However, the magnitude of the spectral changes observed was independent of the the concentration of substrate added. The addition of NADPH to the microsomes-substrate mixture modified the spectral change. Both drugs caused a considerable decrease in thymus weight and the number of thymus lymphocytes, while the alkaline phosphatase activity was enhanced in 5-FU groups, indicating that the agents cause a significant involution of the thymus. Decrease in the total number of the lymphocytes was greater than that in the blood leucocytes.
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PMID:Antitumor agents. I. Effect of 5-fluorouracil and cyclophosphamide on liver microsomes and thymus of rat. 100 1

1. Microsomes prepared from midgut tissue of Manduca sexta by differential centrifugation are a heterogeneous population of vesicles. 2. Upon centrifugation of microsomes in a sucrose gradient of 30%, 15% and 10%, specific activity of cytochrome P-450 catalyzed O-demethylation of p-nitroanisole (a marker enzyme for endoplasmic reticulum) was increased 2.5 to 3.5-fold in the 15% fraction. 3. Specific activities of alkaline phosphatase and leucine aminopeptidase (marker enzymes for brush border membranes) were increased 3.1 to 5.7-fold in the pellet. 4. Differential centrifugation is a useful step in the purification of cytochrome P-450 enzymes.
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PMID:Separation of cytochrome P-450 containing vesicles from the midgut microsomal fraction of Manduca sexta. 135 31

Duchenne muscular dystrophy (DMD) is a fatal disease for which there is no effective treatment. The cause of death in patients with DMD is often cardiovascular and pulmonary dysfunction. This clinical observation, combined with experimental findings, suggests that other non-muscle organ systems may be affected in the dystrophic disease state. To test this hypothesis, the present study investigated liver and kidney function in the mdx mouse. Serum chemistries and the hepatic cytochrome P-450 system in normal and dystrophic mdx mice were investigated at two different ages. Increases in serum lactate dehydrogenase (LDH), alkaline phosphatase (AP), aspartate transaminase (AST), and cholesterol levels, combined with an increase in liver weight and a decrease in cytochrome P-450, suggests the possibility of hepatic dysfunction. Increases in serum uric acid and phosphorus, and decreased kidney weight suggest hepatic dysfunction.
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PMID:Serum and organ indices of the mdx dystrophic mouse. 143 89

To assess whether potential toxic interactions occur between ethanol and allyl alcohol or carbon tetrachloride following subacute, concurrent chemical exposure, male Fischer 344 rats, approximately 70 d of age, were given ethanol at 0, 0.05, 0.1, 0.2, or 0.5 ml/kg in corn oil daily by gavage for 14 d (ETOH group), or the same levels of ethanol with 21 mg allyl alcohol/kg (ALAC group), or the same levels of ethanol with 20 mg carbon tetrachloride/kg (CCL4 group). Hepatic response was assessed 24 h after the last dose. Interactions were evaluated by comparing the ETOH group with either the ALAC group or the CCL4 group using multivariate analysis of variance procedures. No statistically significant interaction was seen between the ETOH group and the ALAC group at the dosages used. Although an interaction between ethanol and carbon tetrachloride given simultaneously was not statistically significant, a small interactive effect on weight gain from d 0 to termination was apparent (p = .057). Exposure to ethanol alone resulted in a concentration-dependent decrease in absolute and relative liver weight, with a threshold between 0.05 and 0.1 ml/kg. There was no histopathological evidence of hepatic damage with ethanol alone, and no effect on hepatic cytochrome P-450 and glutathione levels or on serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALK). Exposure to allyl alcohol alone resulted in significant increases in absolute and relative liver weights, liver glutathione, and periportal hepatocellular vacuolar degeneration. Exposure to carbon tetrachloride alone resulted in significant increases in absolute and relative liver weight, serum levels of ALT, AST, and ALK, and centrilobular hepatocellular vacuolar degeneration and necrosis. These observations indicate that subacute, concurrent exposure of ethanol with carbon tetrachloride or allyl alcohol at ethanol levels comparable to those reported in gavage vehicles did not result in interactive toxicity.
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PMID:Hepatotoxic interactions of ethanol with allyl alcohol or carbon tetrachloride in rats. 152 9

We examined how total blockage of biliary excretion, the major pathway through which cholesterol and bile acids are removed from the body, affects liver function, cholesterol and bile acid metabolism and homoeostasis. After 4 weeks of bile-duct ligation, rats showed impaired liver function, as documented by elevations in serum bilirubin and alkaline phosphatase activity. Moreover, bile-duct ligation decreased by about 30% both the amount of microsomal cytochrome P-450 in the liver and the elimination of aminopyrine in vivo, a reliable index in vivo of microsomal mixed-function oxidase activity. Cholesterol and bile acid contents in livers of bile-duct-ligated rats were doubled compared with sham-operated controls. Despite the increase in the contents of cholesterol and bile acids in liver, activities of the respective rate-limiting enzymes, 3-hydroxy-3-methylglutaryl-CoA reductase and cholesterol 7 alpha-hydroxylase, were doubled. Serum concentrations of bile acids and free cholesterol increased 25- and 4-fold respectively. The large increase in serum bile acids was associated with a 380-fold increase in the urinary excretion of bile acids. Although there is a general decrease in cytochrome P-450 content and drug metabolism involving cytochrome P-450-containing hydroxylases, the activity of cholesterol 7 alpha-hydroxylase, also a cytochrome P-450-containing enzyme, is actually increased. These data show that complete obstruction of the bile duct results in the selective impairment of microsomal cytochrome P-450. Increased activity of 7 alpha-hydroxylase, bile acid synthesis and urinary excretion provides an alternative excretory pathway that helps to maintain cholesterol homoeostasis when the biliary excretory pathway is eliminated.
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PMID:Regulation of cholesterol and bile acid homoeostasis in bile-obstructed rats. 174 9

Due to the ubiquitous presence of p-xylene in air and the existing uncertainty regarding its hepatotoxic potential, we examined the effect of acute and short-term exposure to inhaled p-xylene on the liver. Male F-344 rats were exposed to 0 or to 1600 ppm p-xylene, 6 h/d, for 1 or 3 d. Exposure to inhaled p-xylene caused no histopathological evidence of hepatic damage and had little or no effect on the serum levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, ornithine carbamyl transferase, alkaline phosphatase, and total bilirubin. Exposure to p-xylene for 1 or 3 d resulted in an increase in relative liver weight on d 1 post-exposure. The concentration of hepatic cytochrome P-450 was increased by both p-xylene exposure regimens on d 1 postexposure and had returned to control levels by d 3 following the single p-xylene exposure and by d 2 following the 3-d exposure. These observations provide consistent evidence that acute and short-term exposure to 1600 ppm p-xylene by inhalation did not produce overt hepatotoxicity but resulted in a significant increase in the concentration of hepatic cytochrome P-450, the principal enzyme system involved in the metabolic biotransformation of xenobiotics.
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PMID:Assessment of the hepatotoxicity of acute and short-term exposure to inhaled p-xylene in F-344 rats. 200 13

To test further the competence of the cirrhotic liver to metabolize xenobiotics, hepatocytes were isolated from control and CCl4-induced cirrhotic male or female rats. Histologically micronodular cirrhosis was present in all CCl4-treated rats, while control rats had normal livers. Portal perfusion pressure and intrahepatic collagen content were also significantly increased by CCl4 administration. In male rats, no significant differences in levels of circulating transaminases nor in alkaline phosphatase was observed between cirrhotic and control rats, while CCl4-treated females had slightly higher than normal serum transaminase levels at the time of the studies. Hepatocytic cytochrome P-450 and basal xenobiotic biotransformation were unaffected by micronodular cirrhosis in both genders; calculation of the aminopyrine and 7-ethoxycoumarin intrinsic clearances (Cli) revealed, however, a slightly decreased transformation potential in hepatocytes obtained from cirrhotic females, a phenomenon not observed in cirrhotic male rats. It is speculated that the observed reduction in Cli may have been independent of cirrhosis per se, owing to the perduring cytotoxic effect of CCl4 as evidenced by the higher than normal level of transaminases in female rats. Finally, male rats were subjected to in vivo administration of phenobarbital or 3-methylcholanthrene; both compounds led to significant induction of the mixed-function oxidase system, which was similar in magnitude and in selectivity in control and cirrhotic rats as illustrated by calculation of the Michaelis-Menten kinetic parameters for aniline p-hydroxylation, aminopyrine-N-demethylation, 7-ethoxycoumarin-O-deethylation, and p-nitrophenol UDP-glucuronyl transferase. We conclude that in well-established but compensated and hepatolysis-free micronodular cirrhosis, hepatocytes are fully able to transform xenobiotics and to respond normally and selectively to inducers of drug metabolism.
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PMID:Unimpaired induction of drug-metabolizing enzymes in hepatocytes isolated from rats with micronodular cirrhosis. 205 6

Loss of calcium regulation across the plasma membrane of hepatocytes is responsible for irreversible cell damage by CCl4. The mode of action of colchicine in CCl4 acute liver damage is not completely understood. We followed the time courses of the changes in lipoperoxidation, the activities of liver plasma membrane Ca2(+)-ATPase, gamma-glutamyl transpeptidase and alkaline phosphatase, as well as the time courses of serum markers of liver damage in rats acutely intoxicated with CCl4. We assessed the effects of colchicine in this model and evaluated the effect of this drug on liver cytochrome P-450. Increased lipoperoxidation is the earliest and shortest lasting effect of CCl4 in the liver and is followed by a decrease in the activities of plasma membrane-bound enzymes. The alterations in serum enzymes showed a slower onset and were more protracted. Colchicine pretreatment produced a small decrease in cytochrome P-450 in the liver but completely prevented most of the changes produced by CCl4 in lipoperoxidation, liver plasma membrane enzyme activities and serum enzyme activities. We conclude that CCl4 metabolites trigger lipoperoxidation and then produce a longer lasting change in the plasma membrane, which thus allows calcium accumulation. Colchicine prevents the early mechanisms of CCl4 damage, and its effect on cytochrome P-450 perhaps plays only a contributory role.
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PMID:CCl4-induced lipoperoxidation triggers a lethal defect in the liver plasma membranes. 213 83

The enzyme activities, which are influenced by the vitamin C level in tissues, were measured to evaluate the vitamin C activity of erythorbic acid (ErA) in guinea pigs administered ErA. Guinea pigs were divided into two groups: animals in one group (control group) were administered 1, 5, and 100 mg/day ascorbic acid (AsA) and those in the other group (supplemented group) were administered 1, 5, 20, and 100 mg/day ErA for 16 days. At the end of the experimental period, they were sacrificed, blood was collected, and their livers were removed. The activities of liver aniline hydroxylase, of liver acid phosphatase, and of serum alkaline phosphatase, and the content of liver cytochrome P-450 were assayed. The activities of aniline hydroxylase and serum alkaline phosphatase and the content of liver cytochrome P-450 of the guinea pigs administered 1 mg ErA were lower than those of the guinea pigs administered 1 mg AsA. However, the enzyme activities and liver cytochrome P-450 content in the guinea pigs administered 5 mg or more of ErA were similar in level to those in the guinea pigs administered 5 mg AsA. These results suggested that administration of a considerably high amount of ErA to guinea pigs showed a similar vitamin C activity to that of AsA, which might suggest that vitamin C activity of ErA may be more than one-twentieth that of AsA, as has been generally believed.
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PMID:Net vitamin C activity of erythorbic acid in guinea pigs. 229 26


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