Search results for "microsomes"
showing 10 items of 193 documents
A time course investigation of vitamin A level and lipid composition of the liver endoplasmic reticulum in rats following treatment with congeneric p…
1990
Abstract The drug metabolizing enzyme activities, the vitamin A content and the fatty acid composition in the endoplasmic reticulum membrane were studied in rat liver after a single injection of the polychlorobiphenyls (PCBs) 3,3′,4,4′-tetrachlorobiphenyl [(3,4)2Cl] or 2,2′,4,4′,5,5′-hexachlorobiphenyl [(2,4,5)2Cl], 300 μ mol/kg each. The microsomal vitamin A level was markedly lowered 3 days after treatment with (3,4)2Cl, a coplanar type inducer of cytochrome P-450. A marked increase in microsomal AHH and UDPGT activities occurred within 3 days after injection of (3,4)2Cl whereas (2,4,5,)2Cl treatment enhanced APDM activity only. Arachidonic, stearic and linoleic acid microsomal contents w…
Effect of onion consumption by rats on hepatic drug-metabolizing enzymes
2001
Fruits and vegetables or their natural constituents which increase detoxication enzymes and/or reduce activating enzymes are considered as good candidates to prevent chemically-induced carcinogenesis. In this study, rats were fed a diet supplemented with 20% onion powder for 9 days. Several cytochrome P450 (CYP)s enzymes (CYP 1A, 2B, 2E1, 3A), which are involved in carcinogen activation, were determined by measuring their enzyme activities using specific substrates. In addition, phase II enzymes activities such as UDP-glucuronosyltransferase (UGT) and glutathione S-transferase (GST), involved in detoxication of carcinogens, were measured. Protein levels of CYPs and GST A1/A2, A3/A5, Ml, M2 …
Purification of rat liver epoxide hydratase to apparent homogeneity.
1975
Epoxide hydratase (EC 4.2.1.63) is a microsomal enzyme which catalyses the conversion of epoxides to trans-dihydrodiols. Epoxides, produced by the action of microsomal monooxygenases (EC 1.14.1.1) from aromatic and olefinic compounds, are thought to be responsible for many of the harinful effects of polycyclic hydrocarbons and related compounds. Thus epoxide hydratase, together with glutathione 9transferases, (EC 2.5.1.18) may play an important role in the removal of carcinogenic and cytotoxic metabolites (for reviews see [l-3]). It has been reported [4,5] that dihydrodiols formed from some polycyclic hydrocarbons (benz(a)anthracene and benzo(a)pyrene) are reactivated by the microsomal mono…
Reduction of benzo(a)pyrene mutagenicity by dihydrodiol dehydrogenase
1979
THE enigma of how inert chemicals can exert potent mutagenic, carcinogenic, allergenic and cytotoxic effects has been much debated. It has been learned that such compounds are metabolically converted to chemically reactive species1. In the case of aromatic or olefinic compounds, monooxygenases located in the membranes of the cell can transform these compounds into epoxides2–5 which by virtue of electrophilic reactivity can bind chemically to cellular macromolecules such as DNA, RNA and proteins, thereby disturbing biochemical control mechanisms and leading to the above mentioned toxic effects. The same membranes in which such epoxides are produced possess an enzyme, epoxide hydratase, which…
EFFECTS OF DIETARY 18:3 N-3 TRANS ISOMERS ON THE ?6 DESATURATION OF ?-LINOLENIC ACID
1995
Trans isomers of polyunsaturated fatty acids (PUFA) are formed during heat treatment of oils. In the present work, the effect of dietary geometrical isomers of α-linolenic acid (18:3 n-3) on the Δ6 desaturation of all cis 18:3 n-3 was investigated, using rat liver microsomes. The desaturation rates were higher in microsomes from animals fed a cis n-3 deficient diet, as compared to those from the control group or those from rats fed 18:3 n-3 and its trans isomers. These data and the incorporation of long chain trans PUFA in microsomal lipids suggest that geometrical isomers of 18:3 n-3 are probably slowly desaturated and elongated into long chain trans polyunsaturated fatty acids compared to…
In vitro glucuronidation of 7-hydroxycoumarin derivatives in intestine and liver microsomes of Beagle dogs
2019
Beagle dog is a standard animal model for evaluating nonclinical pharmacokinetics of new drug candidates. Glucuronidation in intestine and liver is an important first-pass drug metabolic pathway, especially for phenolic compounds. This study evaluated the glucuronidation characteristics of several 7-hydroxycoumarin derivatives in beagle dog's intestine and liver in vitro. To this end, glucuronidation rates of 7-hydroxycoumarin (compound 1), 7-hydroxy-4-trifluoromethylcoumarin (2), 6-methoxy-7-hydroxycoumarin (3), 7-hydroxy-3-(4-tolyl)coumarin (4), 3-(4-fluorophenyl)coumarin (5), 7-hydroxy-3-(4-hydroxyphenyl)coumarin (6), 7-hydroxy-3-(4-methoxyphenyl)coumarin (7), and 7-hydroxy-3-(1H-1,2,4-t…
Carboxyl nonsteroidal anti-inflammatory drugs are efficiently glucuronidated by microsomes of the human gastrointestinal tract.
2004
Limited studies have been carried out on the biotransformation of carboxyl nonsteroidal anti-inflammatory drugs (NSAIDs) in the liver. However, the role of the intestine in NSAID metabolism has not been investigated. In this report, the contribution of UDP-glucuronosyltransferases (UGTs) in the human gastrointestinal (GI) tract from five donors to the glucuronidation of the NSAIDs, RS-ketoprofen, S-naproxen, RS- and S-etodolac, was investigated. UGT activity and, for some donors, mRNA levels were evaluated. All NSAIDs were glucuronidated throughout the GI tract; however, glucuronidation was low in stomach and duodenum as compared to the remainder of the intestine. RT-PCR analysis demonstrat…
Focal elevation of liver microsomal epoxide hydrolase in early preneoplastic stages and its behaviour in the further course of hepatocarcinogenesis.
1981
Abstract Treatment of rats with N-nitrosomorpholine (NNM) for 7 weeks led to a focal increase in liver microsomal epoxide hydrolase (EH) as early as 2 weeks after withdrawal of the carcinogen. This treatment also leads to hyperplastic nodules and liver tumors, but much later. At the same early time point, ATPase activity was decreased in the same islands. Most of these areas already had increased γ-glutamyltranspeptidase activity. The increase in EH at this early time point was more distinct than the decrease in ATPase which has thus far been considered a suitable marker of the earliest stages in hepatocarcinogenesis. The focal increase in EH was also observed in all benign hepatomas, but n…
The induction of hepatic microsomal metabolism in rats following acute administration of a mixture of polybrominated biphenyls.
1976
Abstract Firemaster BP6, a mixture of polybrominated biphenyls (PBBs), was administered to female Sprague-Dawley rats (170–180 g) as a single ip injection at 25 and 150 mg/kg. Other animals received phenobarbital (PB), 3-methylcholanthrene (3MC), or PB and 3MC together. Animals were killed at intervals of 12, 24, 48, 192, and 336 hr after treatment with PBBs, or 24 hr after PB, MC, or PB-MC, and various hepatic microsomal parameters were measured. After 150 mg/kg of PBBs, cytochrome P450 concentrations reached a maximum by 48 hr (225% of control), then remained elevated through 336 hr. A similar pattern of induction was observed for epoxide hydratase and aniline hydroxylase activities. In c…
SEX DIFFERENCES IN THE PATTERN OF CYTOCHROMES P-450 IN RAT LIVER MICROSOMES
1977
ABSTRACT A number of sex differences in the spectral and enzymic properties of rat liver microsomes have been observed which may reflect differences in the population of hepatic cytochromes P 450 of male and female rats: 1. a blue shift in the spectrum of the reduced P 450-CO complex in females as compared to males, 2. lower ΔA max values in the binding of metyrapone to reduced microsomes in females as compared to males, 3. a higher proportion of 2-hydroxylation in the metabolism of biphenyl in females as compared to males, 4. preferential inhibition of ethoxycoumarin deethylation, benzpyrene hydroxylation and biphenyl-4-hydroxylation by α-naphthoflavone in females but by metyrapone in male…