Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of low and high doses of three anticancer agents, cyclophosphamide, vincristine, and prednisone (given individually or in various combinations), on oxidative and conjugation pathways were studied in Sprague-Dawley male rats. Cyclophosphamide used alone at low doses decreased aniline hydroxylase and ethylmorphine demethylase activities by about 20% and at high doses produced a 30%-50% decrease in the specific activities of several microsomal mixed-function oxygenase activities, in the contents of cytochromes P-450 and b5, and in the magnitudes of type I and II drug-binding spectrum. The levels of microsomal glucouronidase, glucuronyl transferase, and sulfatase per gram of liver were also decreased (30%-50%) by the high dose of cyclophosphamide. The high dose of cyclophosphamide in conjunction with either vincristine or prednisone also produced a noticeable decrease in several activities tested; however, when cyclophosphamide was given at either low or high doses in combination with vincristine and prednisone, the activities tested were comparable to those seen in untreated controls. The mechanism of this protection is presently unknown. Vincristine, at both low and high doses, produced little effect on oxidative pathways; however, at low doses it caused a significant increase (80%) in the specific activity of hepatic microsomal sulfatase. This effect was also discernible when vincristine was given in combination with cyclophosphamide and prednisone. Other than producing a 15% decrease in liver weight and a 40% decrease in the specific activity of microsomal glucuronidase, the high dose of prednisone used had no effect on various activities tested. Results of these studies indicate a potential for drug interaction among anticancer agents and supportive drugs used in combination cancer chemotherapy.
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PMID:Studies of the effects of cyclophosphamide, vincristine, and prednisone on some hepatic oxidations and conjugations. 101 65

Dibutyryl cyclic adenosine 3':5'-monophosphate (DBcAMP) has been reported to cause numerous alterations in the activity of hepatic monooxygenase enzymes following in vivo administration or in vitro addition to intact liver preparations. In the present report the effect of the nucleotide on metabolism of p-nitroanisole (pNA) and aniline was studied in isolated rat hepatocytes. Initial studies indicated that in vitro addition of DBcAMP to hepatocytes increased metabolism of both pNA and aniline as determined by the production of oxidized metabolites, p-nitrophenol (pNP) and p-aminophenol, respectively. After enzymatic hydrolysis with beta-glucuronidase and arylsulfatase, it was determined that DBcAMP had increased accumulation of pNP formed from pNA by inhibiting further metabolism via conjugation reactions. Further studies using pNP directly as substrate confirmed the finding and revealed that glucuronidation was more sensitive to the inhibitory effect of DBcAMP than was sulfation. The 8-bromo derivative of cAMP was more potent than DBcAMP at inhibiting glucuronidation, whereas cyclic AMP and dibutyryl cyclic guanosine 3':5'-monophosphate were without effect. Noncyclic adenine nucleotides (ATP, ADP, AMP) also altered pNA and pNP metabolism. ATP and ADP increased pNP accumulation from pNA while ATP and AMP inhibited glucuronidation of pNP. DBcAMP was further found to decrease UDP-glucuronic acid levels in a concentration-dependent manner without disrupting the redox state (NAD+/NADH) in hepatocytes. The data suggest that adenine nucleotides exert a nonspecific inhibition upon glucuronidation and sulfation reactions.
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PMID:Inhibition of glucuronidation and sulfation by dibutyryl cyclic AMP in isolated rat hepatocytes. 287 57

A method is described for preparing and maintaining an isolated perfused and ventilated mouse lung. The preparation is especially suited for studying xenobiotic metabolism or toxicological interactions, in a species with a broad spectrum of studies in pulmonary toxicology. The preparation is viable with respect to drug metabolism for up to two hours, as judged from studies of aniline oxidation to p-aminophenol. With [14C]-benzo(a)pyrene as substrate for the lungs of male ICR Swiss mice, the major ethyl acetate-extractable metabolites are the 3-hydroxy, 9,10-dihydrodiol, 7,8-dihydrodiol, and 4,5-dihydrodiol derivatives. The rates of individual BaP metabolite production are increased in lungs from mice pretreated with Aroclor 1254 or beta-naphthoflavone, substances known to induce increased synthesis of cytochrome P-450. Small amounts of water-soluble BaP metabolites were hydrolyzed by beta-glucuronidase and aryl sulfatase, suggesting the presence of enzymes required for these conjugations. These results support the existence of significant cytochrome P-450-dependent and conjugative BaP metabolism in the intact mouse lung, similar to that examined in other species, and capable of contributing to the systemic metabolism of this carcinogen.
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PMID:Benzo(a)pyrene metabolism in the isolated perfused mouse lung. 631 13