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

Ebselen is a seleno-organic compound that inhibits oxidative stress by lipid peroxidation through a glutathione peroxidase-like activity. We studied the effect of ebselen on the expression of hepatic drug-metabolizing enzymes in rats with deoxycholic acid-induced liver injury. Hydrophobic bile acids, such as deoxycholic acid, are known to cause cholestatic liver injury, and it was reported that expression of hepatic cytochrome P-450 (CYP) was reduced by deoxycholic acid administration in rats. Hydrophobic bile acids induce lipid peroxidation in the liver, and this may be one mechanism of the development of liver injury. In the present study, we investigated the effect of ebselen (30 mg/kg/day for 10 days) on rats ingesting deoxycholic acid (1% of diet for 10 days). Deoxycholic acid decreased levels of CYP1A1, 2B1, 2E1 and 3A2 to 34, 58, 62 and 37% of control values, respectively, and increased serum alkaline phosphatase (ALP) and alanine aminotransferase (ALT) activities to 1.8 and 8.6 times the levels of controls, respectively. Administration of ebselen with deoxycholic acid prevented the decreases in levels of CYP1A1 and 3A2 (86 and 65% of control, respectively) and the increases in serum ALP and ALT activities (1.4 and 1.9 times of control, respectively) caused by deoxycholic acid. These results indicate that ebselen may have a protective effect against hydrophobic bile acid-induced liver injury.
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PMID:Ebselen protects against the reduction in levels of drug-metabolizing enzymes in livers of rats with deoxycholic acid-induced liver injury. 1242 Jul 94

Ginsan, a polysaccharide isolated from Panax ginseng, has been shown to be a potent immunomodulator, producing a variety of cytokines such as TNF-alpha, IL-1, IL-2, IL-6, IL-12, IFN-gamma and GM-CSF, and stimulating lymphoid cells to proliferate. In the present study, we analyzed some immune functions 1st-5th days after ginsan i.p. injection, including the level of non-protein thiols (NPSH) as antioxidants, heme oxygenase (HO) activity as a marker of oxidative stress, zoxazolamine-induced paralysis time and level of hepatic cytochrome P-450 (CYP450) as indices of drug metabolism system, and activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, and albumin level as indicators of hepatotoxicity. Ginsan in the dose of 100 mg/kg caused marked elevation (1.7 to approximately 2 fold) of HO activity, decrease of total CYP450 level (by 20-34%), and prolongation of zoxazolamine-induced paralysis time (by 65-70%), and showed some differences between male and female mice. Ginsan treatment did not seem to cause hepatic injury, since serum AST, ALT, and ALP activities and levels of total bilirubin and albumin were not changed.
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PMID:Effects of polysaccharide ginsan from Panax ginseng on liver function. 1520 59

To investigate the presence and localization of a variety of xenobiotic biotransforming isozymes of the cytochrome P-450 superfamily in the organogenesis-stage rat conceptal tissue, pregnant female rats were dosed with one of two inducing agents, 3-methylcholanthrene [3MC, 40 mg/kg body weight, ip, day 7 post coitum (pc)] and phenobarbital (PB, 40 mg/kg, ip, days 5, 6, 7 and 8 pc), or with their vehicles (3MC, olive oil; PB, 0.9% NaCl) as controls. The conceptuses were allowed to grow either in vivo, or in vitro, using the whole embryo culture system, from days 9.5 to 11.5 pc. The embryos and isolated visceral yolk sacs were submitted to immunohistochemical investigation using light microscopy. The livers of the dams served as positive controls. Polyclonal and monoclonal antibodies raised against a variety of cytochrome P-450 isozymes were used in the alkaline phosphatase-anti-alkaline phosphatase enzyme immune complex method. All pre-induced dam livers showed positive staining with all polyclonal and monoclonal antibodies tested. The presence of P450IA1 was detected in the visceral yolk sac of both ex vivo and cultured conceptuses, preinduced in utero with 3MC, with the appropriate polyclonal antibodies but not with the monoclonal antibodies. P450IIB1/2 was detected in the visceral yolk sac of both ex vivo and cultured conceptuses, pre-induced in utero by phenobarbital, with the appropriate polyclonal antibodies, but not with the monoclonal antibodies. No staining was seen in any embryo proper, with any vehicle-treated conceptal tissue, or with antibodies raised against P-450s IIE1, IIIA or IVA. Our results support the hypothesis that the organogenesis-stage rat conceptus contains, in the visceral yolk sac, a 3MC-inducible P-450 isozyme similar, but not identical, to adult IA1. They also provide evidence that a PB-inducible isozyme similar, but not identical, to adult IIB1/2, is present in the visceral yolk sac at this stage of conceptus development.
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PMID:An immunohistochemical investigation into the presence and localization of cytochrome P-450 isozymes in organogenesis-stage rat conceptal tissue. 2073 68

It is well known that schistosomal infection and food contamination with aflatoxins caused marked histopathological changes in human liver. This study demonstrates the influence of Schistosoma mansoni infection on the capacity of drug-metabolizing enzymes and in vitro aflatoxin B-1 metabolism in human liver. Clinical data showed an increase in alkaline phosphatase, alanine and aspartate aminotransferase by 82, 74 and 100%, respectively. The activity of NADPH cytochrome C reductase and cytochrome P-450 content were significantly decreased in the liver of schistosomal patients by 70 and 52% respectively. The cytochrome b-5 content was also decreased by 61%. Aflatoxin B-1 tris-diol could not be detected using the microsomal fractions of the schistosomal group relative to the control group. The content of aflatoxin Q(1) metabolite produced by microsomal fractions of schistosomal patients increased by 308%. There was no difference in the formation of aflatoxin M(1) between the two groups. These observations indicate that Schistosoma mansoni infection might potentiate the deleterious effects of environmental carcinogens.
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PMID:Influence of Schistosoma mansoni infection on carcinogen-metabolizing capacities and in vitro aflatoxin B-1 metabolism in human liver. 2159 52


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