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)

In the present study, it was investigated whether the prostacyclin derivative Iloprost would protect hepatocytes against CCl4-induced liver injury and which mechanism(s) of hepatocellular pathogenesis might be affected by it. Rats were treated with a single oral dose of CCl4 (2 ml per kg); Iloprost was infused continuously from 2 to 4 hr before intoxication until killing. The following results were obtained. The CCl4-induced release of AST, lactate dehydrogenase and alkaline phosphatase into the serum was reduced by 50 to 70% in rats treated with doses of 0.1 and 0.5 micrograms Iloprost per kg per min. Infusion of 0.02 and 0.004 micrograms Iloprost per kg per min did not affect the CCl4-induced enzyme release into the blood. CCl4 induced the occurrence of aldehydes (products of lipid peroxidation), which were detected by histochemical and biochemical means. At 12, 48 and 72 hr after CCl4, the aldehyde-positive liver section area was about 58, 69 and 16% in rats treated with CCl4 alone, but only about 18, 13 and less than 1% in rats treated additionally with Iloprost. The aldehyde-positive hepatocytes were located predominantly in the centrilobular zone of the liver. At 24 hr the extent of the aldehyde-positive section area was the same in rats with or without Iloprost treatment (about 90%). Biochemical determination, however, revealed that at this time point the malondialdehyde content after Iloprost in rats was about 70% lower than without Iloprost treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Histochemical and biochemical studies on the effect of the prostacyclin derivative iloprost on CCl4-induced lipid peroxidation in rat liver and its significance for hepatoprotection. 246 34

Pretreatment of rats with colchiceine (10 micrograms/day/rat) for seven days protected against CCl4-induced liver damage. CCl4 intoxication was demonstrated histologically and by increased serum activities of alanine amino transferase (ALT), alkaline phosphatase (Alk. Phosph.) gamma glutamyl transpeptidase (GGTP), bilirubins and decreased activity of glucose-6-phosphatase (G-6Pase). Furthermore, an increase in liver lipid peroxidation and a decrease in plasma membrane GGTP and Alk. Phosph. activities were found. Colchiceine increased 1.5-fold the LD50 of CCl4 and prevented the release of intracellular enzymes as well as the decrease in GGTP and Alk. Phosph. activities in plasma membranes. It also completely prevented the lipid peroxidation induced by CCl4 and limited the extent of the histological changes.
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PMID:Protective effect of colchiceine against acute liver damage. 257 11

Aqueous extracts of the aerial parts of Melothria maderasptana and the leaves of Osbeckia octandra have been compared with (+)-3-cyanidanol with regard to their abilities to alleviate carbon tetrachloride (CCl4)-induced liver dysfunction in albino rats by comparing the abilities of these drugs to protect the liver against CCl4-mediated alterations in the liver histopathology and serum levels of aspartate aminotransferase (GOT), alkaline amino-transferase (GPT), and alkaline phosphatase. In both pretreatment and post-treatment (administration of drugs before or after CCl4 treatment) experiments, the most marked rate of recovery of the liver was exhibited by the group of rats treated with Melothria maderaspatana extract. Although the protection offered by (+)-3-cyanidanol and Osbeckia octandra appears to be comparable in post-treatment, Osbeckia was significantly more effective in pre-treatment. From the overall results obtained it appears that the aqueous extracts of Melothria maderaspatana and Osbeckia octandra are both as potent or in some instances (in pretreatment experiments) more potent than (+)-3-cyanidanol. Of the two plants tested under the present experimental conditions used, Melothria maderaspatana appears to be marginally more effective than Osbeckia octandra in protecting the liver against CCl4-induced alterations.
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PMID:An evaluation of the potency of Osbeckia octandra and Melothria maderaspantana as antihepatotoxic agents. 274 29

The effect of Laennec (human placenta hydrolysate) on CCl4-induced acute or chronic liver injury in rats was examined. In the acute liver injury induced by CCl4, 0.5 ml/kg for 4 days, intravenous injection of Laennec increased total protein and decreased nonesterified fatty acid in the liver. Subcutaneous injection of Laennec inhibited the decrease of liver phospholipid by CCl4 administration. Both intravenous and subcutaneous injections of Laennec inhibited the increases of serum transaminase (GOT, GPT) levels caused by CCl4. Furthermore, intravenous Laennec inhibited the increase of serum alkaline phosphatase level. Pathological examinations of the liver indicated that both intravenous and subcutaneous injections of Laennec inhibited the loss of cytoplasma and nuclei, vacuolation, swelling and necrosis in the centrizonal hepatocytes caused by CCl4. Intravenous and subcutaneous injection of Laennec also inhibited the increases of GOT and GPT levels in rats with chronic liver injury caused by CCl4, 0.5 ml/kg for 7 weeks. Both intravenous and subcutaneous injections of Laennec minimized the pathological changes of the liver by CCl4 such as vacuolation, necrosis and swelling of nuclei, but did not inhibit the formation of pseudolobules. Thus, no therapeutic difference was noted between intravenous and subcutaneous injections of Laennec.
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PMID:[A comparative study of Laennec by intravenous or subcutaneous injection on CCl4-induced acute or chronic liver injury in rats]. 280 70

A detailed analysis is presented of the time changes in the development of liver damage 6, 12, 24, 48 and 72 hours after i.p. administration of carbon tetrachloride [CCl4] in a dose of 0.75 ml, i.e. 1 200 mg/kg body weight to rats of both sexes. The severity of liver damage was assessed from the histological and biochemical changes of AST, ALT, alkaline phosphatase and GMT serum activity. From our experiments it follows that in male rats the level of transaminases increases earlier than in female rats, as early as 6 h after the administration of CCl4, reaching a maximum 12 h later. These changes prevail for a longer time period, the level of transaminases remaining increased even 72 h after CCl4 administration. In female rats the biochemical changes occur later reaching the maximum elevation of AST and ALT 24 h after CCl4 administration. The values slowly return to normal after 48 h, and after 72 h the levels of transaminases are identical with the control group. The above given biochemical results are in good agreement with the histological findings demonstrating a higher regenerative activity in female rats. This finding was also proved by specific liver DNA activity assay.
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PMID:The time course of biochemical and histological changes following carbon tetrachloride-induced liver damage in rats of both sexes. 286 69

In a short-term study the response of ornithine carbamyl transferase (OCT) was compared to that of glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) in the serum of rats after treatment with single doses of carbon tetrachloride (CCl4). Furthermore, the sensitivity of gamma-glutamyl transpeptidase (gamma-GT) was studied in comparison to alkaline phosphatase (AP) and bilirubin. After dosing 100 microliter CCl4/kg, the response of OCT activity was 10- and 20-times higher than that of GOT and GPT, respectively. At 300 microliter/kg we observed an increase of up to 17- and 34-times of GOT and GPT activities. Maximal elevation of gamma-GT activity was about twice that of AP and of the bilirubin content. Moreover, the variability of the gamma-GT activities was found to be considerably higher, than that of AP and bilirubin levels. These results indicate, that OCT is a useful parameter to detect hepatic parenchymal injury, whereas gamma-GT cannot be proposed as an alternative to AP and bilirubin.
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PMID:Comparative study on the sensitivity of several serum enzymes in detecting hepatic damage in rats. 286 47

Selected serum parameters (enzyme activities and triglycerides) and liver glutathione and vitamin C concentrations were measured in English sole (Parophrys vetulus) after i.p. injection of carbon tetrachloride (CCl4), a hepatotoxin in fish. Serum lactate dehydrogenase (LDH), alkaline phosphatase (AP) and glutamate dehydrogenase (GDH) activities and the concentration of triglycerides increased in a dose-dependent manner 24 hr post injection. Concentrations of glutathione (reduced and oxidized) and ascorbic acid (vitamin C) in liver did not change in response to CCl4 toxicity 24 hr post injection. These studies indicate that serum AP activity and triglyceride concentrations can be useful in assessing the effects of CCl4-induced liver toxicity in this species of marine fish. Serum LDH and GDH activity should be used with some caution in assessing liver damage in English sole, as other tissues represent more likely sources for serum activity. The levels of liver antioxidants do not appear to be significantly affected, 24 hr post injection, by this particular hepatotoxin.
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PMID:Hepatotoxic effects of CCl4 on English sole (Parophrys vetulus): possible indicators of liver dysfunction. 287 55

We have compared the effects of BW755C, a dual inhibitor of the arachidonic acid cyclo-oxygenase and lipoxygenase, with the effects of colchicine and indomethacin on the reversion of the biochemical and histochemical signs of rat liver cirrhosis. This was induced by i.p. administration of CCl4 for 11 weeks. At this point the rats were divided into four groups (10 animals each). CCl4 administration was continued for one month along with either colchicine, BW755C or indomethacin. No additional treatment was given to the control group. BW755C consistently improved all the parameters studied. Although colchicine also improved all but two markers (serum ALT activity and serum proteins) it ranked lower than BW755C in most of them. Indomethacin only modified favourably serum alkaline phosphatase activity, serum proteins, cholesterol and bilirubins and liver collagen content. The effects of BW755C could be mainly attributed to the inhibition of the lipoxygenase pathway. A common feature of colchicine, adrenal steroids and BW755C was the ability to inhibit the formation of leukotriene and other lipoxygenase products. The possibility that this property might contribute to their anti-cirrhotic actions is discussed.
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PMID:Reduction of apparent indicators of liver cirrhosis in rats by the arachidonate lipoxygenase inhibitor BW755C. 288 11

The enzymic tests and radionuclide hepatography were used to study and compare liver function after rabbits were exposed to tetrachloromethane poisoning. The activity of serum enzymes of cholinesterase, alkaline phosphatase, aldolase and leucine aminopeptidase was determined. Hepatography was made with the use of 198Au-colloid with an activity 0.74 MBC. The enzymic tests were demonstrated to be more sensitive than radionuclide hepatography in detecting the earliest parenchymatous lesions in the liver. The data obtained correlate with the data of the pathohistological examinations, which demonstrated the presence of marked vacuole parenchymatous fatty dystrophy. The authors recommend that the enzymic tests should be used for detecting early hepatic lesions induced by tetrachloromethane.
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PMID:[Potentials of enzyme tests and radioisotope hepatography in detecting early functional changes in the liver]. 298 74

The influence of 5,10-dihydroindeno[1,2-b]indole (indenoindole) on carbon tetrachloride (CCl4)-mediated hepatotoxicity and lipid peroxidation were examined. Indenoindole (25 mg/kg body weight) ameliorated the increase in liver enzymes appearing in the plasma 24 hr after CCl4 administration, with about a 63% reduction for alanine transaminase, 56% for ornithine transcarbamylase and 84% for alkaline phosphatase. Indenoindole also partially prevented, in a dose-dependent fashion, the decrease in hepatic cytochromes P-450, total tissue reducing equivalents and hepatic ascorbate levels resulting 4 hr after CCl4 administration. In a homogeneous chemical system consisting of purified soybean phospholipid substrate in chlorobenzene, azobisisobutyronitrile-initiated lipid peroxidation was inhibited by indeno-indole, with 50% inhibition occurring at about 17 microM. Inhibition by indenoindole of iron-ascorbate-initiated lipid peroxidation in aqueous buffer containing phospholipid vesicles was about tenfold more efficient, with 50% inhibition occurring at about 1.5 microM. Presumably, this was due to the increased concentration of indenoindole in the membrane of the phospholipid vesicle. The efficiency of inhibition of lipid peroxidation was in the order of indenoindole = butylated hydroxytoluene (BHT) greater than alpha-tocopherol much greater than indole greater than indene. These 50% inhibition values of lipid peroxidation for these compounds were similar in an assay system composed of NADPH-fortified mouse-liver microsomes initiated with CCl4. For indenoindole, the 50% inhibition value (1.3 microM) was more than two orders of magnitude less than the spectral binding constant for indenoindole to mouse-liver cytochrome P-450 (Kd = 236 microM), implying that the partial inhibition of metabolic activation of CCl4 was not responsible for the inhibition of lipid peroxidation observed with indenoindole in this system. It appears that indenoindole may trap reactive radicals and inhibit lipid peroxidation in vitro. Regardless of whether inhibition is at the level of scavenging CCl4 metabolite radicals, or lipid radicals in membranes, radical trapping provides a plausible mechanism by which this compound inhibited CCl4 hepatotoxicity.
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PMID:Protection against carbon tetrachloride hepatotoxicity by 5,10-dihydroindeno[1,2-b]indole, a potent inhibitor of lipid peroxidation. 316 51


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