Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elaidic and linoleic acids were administered at doses of 40 and 200 mg/kg i.p. every second day for 4 weeks to rats fed a fat-free diet. The fatty acids had only a slight effect on the weight gain of the animals. The amount of microsomal protein was slightly decreased with the higher dose of linoleic acid. The higher dose level of both fatty acids decreased the microsomal phospholipid content. The relative amounts of microsomal phospholipid fatty acids were also altered due to fatty acid administration. The activity of microsomal NADPH cytochrome c reductase and microsomal cytochrome P-450 contents were decreased by the higher dose of linoleic acid. The hepatic aryl hydrocarbon hydroxylase and p-nitroanisole O-demethylase activities decreased in fatty acid-treated rats. The UDP-glucuronosyltransferase activity was also lowered after the fatty acid administration. The results suggest that fatty acid-induced changes in the activities of drug-metabolizing enzymes may be due to the microenvironmental changes of membrane-bound enzymes.
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PMID:Regulation of hepatic drug metabolism by elaidic and linoleic acids in rats. 41 54

Male rats were fed a cholesterol-free diet for 5 weeks, followed by a 2% cholesterol diet for 4 weeks. Another group of rats was continuously fed a cholesterol-free diet. A third group was fed standard pelllets during the whole experiment. Hepatic microsomal protein and cholesterol contents and drug-metabolizing enzyme activities were measured. The cholesterol-rich diet increased microsomal protein content and this increase disappeared after trypsin digestion of microsomal membranes. Microsomal cholesterol content was enhanced three-fold by cholesterol feeding. Cytochrome P-450 concentration, NADPH cytochrome c reductase and aryl hydrocarbon hydroxylase activities showed only minor changes following cholesterol feeding. The p-nitroanisole O-demethylase and ethoxycoumarin deethylase activities were doubled by cholesterol in comparison to cholesterol-free diet. Trypsin digestion activated the UDP-glucuronosyltransferase enzyme eight- to ten-fold on a protein basis. Trypsin treatment increased the cholesterol activation of UDP-glucuronosyltransferase when compared to the activity in native microsomes. The data suggest that dietary cholesterol regulates the cholesterol content of microsomal membranes. The activities of drug-metabolizing enzymes are also altered, possibly due to the compositional changes of the membranes.
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PMID:Dietary cholesterol-induced enhancement of hepatic biotransformation rate in male rats. 70 59

Glucuronidation of 4-nitrophenol, nopol (a monoterpenoid alcohol) and bilirubin, which in the rat, are catalyzed by three different enzymes, has been examined in liver biopsies from patients with various liver diseases, in particular cholestasis. These different activities were not correlated, which strongly suggests that at least three independently regulated forms of UDP-glucuronosyltransferases were present in the microsomes. Non ionic detergents (Triton X100, Emulgen 911) and deoxycholate produced similar activation (more than 2-fold) of the glucuronidation of 4-nitrophenol. Amphipathic substances, such as CHAPS (3-[3-cholamidopropyl-dimethylammonio]-1-propane sulfonate), and lysophosphatidylcholines maximally increased this UDP-glucuronosyltransferase activity, the most potent being oleoyl lysophosphatidylcholine (4-fold increase). Discriminant analysis of the data revealed no correlation between the three different UDP-glucuronosyltransferase activities and the age or sex of the patients. A good correlation was found on multidimensional analysis between form 1 of the enzyme (4-nitrophenol glucuronidation) and, in decreasing order of magnitude, epoxide hydrolase (measured with benzo(a)pyrene-4,5-oxide as substrate), cytochrome P-450, 7-ethoxycoumarin deethylase, aspartate aminotransferase and gamma-glutamyltransferase (r = 0.89); and between Form 3 of the enzyme (bilirubin glucuronidation) and NADPH cytochrome c reductase, alkaline phosphatase, (r = 0.81). These relationships may reflect the differential variation in enzymatic activities in various hepato-biliary diseases.
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PMID:Properties of human hepatic UDP-glucuronosyltransferases. Relationship to other inducible enzymes in patients with cholestasis. 288 32

The genic transfer of the jaundice locus (jj) from the Gunn rat into the inbred RHA/++ rat produced congenic inbred homozygous RHA/jj rats which lacked detectable bilirubin UDP-glucuronosyltransferase activity. Congenic inbred RHA/j+ rats contained half the activity for bilirubin of the RHA/++ strain. Constitutive activities for glucuronidation of sixteen substrates of twenty-one tested were inherited additively. Approximately seven groups were discernible based on the defect in activity for these substrates in the RHA/jj strain. Activity for 1-hydroxybenzo[a]pyrene was, after that for bilirubin, the most severely reduced (188-fold), while no differences in the glucuronidation of three androgens and of the 6-hydroxy-, 10-hydroxy-, and 11-hydroxybenzo[a]pyrenes were observed. The conjugation of other substrates was affected to an intermediate extent. Most of the twenty-one glucuronidating activities were induced by phenobarbital in the RHA/jj strain as well as in the RHA/++ and RHA/j+ strains. Activities for 9-hydroxybenzo[a]pyrene and for the 2-hydroxy- and 4-hydroxybiphenyls were induced such that the defect was overcome, and the RHA/jj had the same level of activity as the RHA/++ strain. Cytochrome p-450 content and cytochrome c reductase and aminopyrine demethylase activities were unaffected in the congenic strains. Cytochrome p-450 content and cytochrome c reductase activity were induced approximately 2.5- and 2.0-fold, respectively, by phenobarbital while aminopyrine demethylase activity was induced about 30% in each strain. The congenic inbred rats should provide a stable and reproducible genetic model for studying defective UDP-glucuronosyltransferase specified by the jaundice (jj) locus.
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PMID:Differences in UDP-glucuronosyltransferase activities in congenic inbred rats homozygous and heterozygous for the jaundice locus. 641 43

In 8-day-old rat pups, pretreatment with a single injection of L-triiodothyronine or L-thyroxine decreased hepatic cytochrome P-450 content, aminopyrine N-demethylase activity and epoxide hydrolase activity but increased hepatic microsomal cytochrome c reductase, 7-ethoxyresorufin O-deethylase and heme oxygenase activities without significantly altering UDP-glucuronosyltransferase activity (towards o-aminophenol) or the microsomal yield. In adult rats of either sex such single injections of L-triiodothyronine failed to significantly alter these enzyme activities. However, multiple injections evoked changes similar to those observed in the pups, in all these enzyme activities, except that 7-ethoxyresorufin O-deethylase activity was slightly decreased rather than increased. These findings demonstrate that: (1) The hepatic monooxygenase system in the rat pup is more responsive to thyroid hormones than that in adult. (2) Thyroid hormones can decrease rat liver cytochrome P-450 content and its dependent monooxygenase activity independently of sexual maturity. (3) Thyroid hormones also decrease hepatic epoxide hydrolase activity in both pups and adults. Thus, hyperthyroidism could render the rat pup more susceptible to hepatotoxicity from electrophilic epoxides which utilize microsomal epoxide hydrolase as the major detoxication pathway.
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PMID:Thyroid hormone-induced changes in the hepatic monooxygenase system, heme oxygenase activity and epoxide hydrolase activity in adult male, female and immature rats. 680 67

Male 3-month-old Wistar rats dosed i.p. with 200 mg/kg of nitromethane or -ethane showed increased acid proteinase activity in the brain 4 h after the injection. The change was accompanied by a marginal increase in the cerebral glutathione concentration. Nitroethane caused enhanced epoxide hydrolase and UDP-glucuronosyltransferase activity in the hepatic microsomal fraction up to 48 h while 7-ethoxycoumarin o-deethylase decreased. These biochemical changes were accompanied by proliferation of smooth endoplasmic reticulum and degranulation and disorganization of the rough endoplasmic reticulum of the nitroethane-exposed liver cells. The hepatic effects of nitromethane were restricted to decreased cytochrome c reductase activity with proliferation of smooth endoplasmic reticulum. The results point at limited peroxidative damage possibly involving reduction of the nitrogroup.
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PMID:Comparison of acute toxic effects of intraperitoneally injected nitromethane and nitroethane in rats. 681 33

Weanling male rats were fed low (LP, 7.5%), standard (SP, 15%) or high protein (HP, 45%) diet for 7 or 14 days ad libitum, and cytochrome c reductase (CYC) and UDP-glucuronosyltransferase (UGT) enzyme activities were determined in intestine, kidney and liver microsomes. HP diet increased CYC activity in intestine and kidney, while LP diet had no effect. Hepatic CYC activity declined with decreasing level of dietary protein. Liver and intestine UGT activities were higher on an LP diet, while kidney enzyme activities were higher on an HP diet. UGT activity toward alpha-naphthol, a UGT1 isoform substrate, was modulated by dietary protein in all tissues, while UGT activity toward 4-hydroxybiphenyl, a substrate for a second UGT1 isoform, was affected only in the intestine. The duration of feeding affected CYC and UGT activities in the intestine. This observation may be explained by the dynamic nature of intestinal tissue. The observation of unique tissue and enzyme responses suggests that generalizations regarding metabolic response to diets based on hepatic studies or single enzymes, may be erroneous.
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PMID:Effect of dietary protein on hepatic and extrahepatic phase I and phase II drug metabolizing enzymes. 896 Jan 51

TNT (2,4,6-trinitrotoluene) was the most common nitro aromatic explosive available in World War II ammunitions. The presence of ordnance dumped at sea might represent a great concern for marine species living close to dumping sites and the toxicological properties of the chemicals released into the marine environments need to be evaluated. The aim of the present study is to investigate the involvement of CYP (cytochrome P450) system in the metabolism of TNT in marine organisms by using the European eel [Anguilla anguilla (Linnaeus, 1758)] as model species. In vivo exposure to sublethal concentration of TNT (0.5, 1 and 2.5 mg/l) leads to a significant decrease in the phase I CYP1A catalytic activities such as EROD (7-ethoxyresorufin-O-de-ethylase) and MROD (7-methoxyresorufin-O-de-ethylase). On the opposite, a significant increase in NADPH cytochrome c reductase activity as well as phase II UDP-glucuronosyltransferase activity is observed. An inhibition at enzyme level is hypothesized for both CYP1A enzymes, also confirmed by a similar decrease observed after in vitro exposure. An active role of NADPH cytochrome c reductase and phase II enzymes in the TNT metabolism may also be hypothesized.
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PMID:The involvement of cytochrome P450 system in the fate of 2,4,6-trinitrotoluene (TNT) in European eel [Anguilla anguilla (Linnaeus, 1758)]. 1707 91