Search results for "Microsome"
showing 10 items of 262 documents
Effect of Antioxidants on Microsomal Enzymes of Rat Liver
1978
Rat diet was supplemented with butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA) or ethoxyquin (EQ) for 14 days, and hepatic microsomal epoxide hydratase (EH) and monooxygenase were subsequently studied in vitro. The antioxidants increased EH activity. The increase was marked with BHT (factor 3) and EQ (factor 4) and was paralleled by an increase in a protein band on SDS polyacrylamide gels which migrated together with purified rat hepatic EH. A slight but nonsignificant increase in cytochrome P450 content and a moderate increase in ethoxycoumarin deethylation and cytochrome b5 content was also observed while aryl hydrocarbon hydroxylase (AHH) activity was not elevated. Irrever…
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…
Relationship between rat liver microsomal Δ6 and Δ5 desaturase activities and fatty acid composition: comparative effects of coconut and salmon oils …
1992
International audience; The aim of this work was to compare the effects of coconut and salmon oils on rat liver microsomal Δ6 and Δ5 desaturations, during protein restriction. A higher Δ6 desaturase activity was noted in rats fed the low-protein coconut oil diet, in comparison with that occurring in rats fed either a low-protein or normal-protein salmon oil diet. No variation was observed in Δ5 desaturase activity or in 20:4n-6/ 18:2n-6 ratio. The fatty acid composition of liver microsomal phospholipids provided evidence of higher levels of 20:5n-3 and 22:6n-3 in the normal-protein salmon oil group, when compared with the low-protein salmon oil group. No influence of experimental diets on 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…
Expression of R-3-hydroxybutyrate dehydrogenase, a ketone body converting enzyme in heart and liver mitochondria of ruminant and non-ruminant mammals
1992
1. The properties of rat liver and bovine heart R-3-hydroxybutyrate dehydrogenase (BDH) have been extensively studied in the past 20 years, but little is known concerning the biogenesis and the regulation of this dehydrogenase over different species. 2. In addition, controversial results were often reported concerning the activity, the level and the subcellular location of this enzyme in ruminants. 3. BDH activity found in liver and kidney mitochondria from ruminants (cow and sheep) is low, while it is much higher in rat. 4. However, the enzyme activity is detected in microsomes and in cytosol of liver and of kidney cells from ruminants. These activities are not correlated to ketonaemia lev…
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…
Covalent Protein Binding of Vinyl Chloride Metabolites During Co-Incubation of Freshly Isolated Hepatocytes and Hepatic Sinusoidal Cells of Rats
1983
Proteins of isolated rat hepatic sinusoidal cells incubated with 14C-vinyl chloride, rat liver microsomes and an NADPH-regenerating system were alkylated by vinyl chloride metabolites formed by microsomes. This suggests that reactive vinyl chloride metabolites can penetrate sinusoidal cells. Protein alkylation in isolated hepatic sinusoidal cells was higher when these were co-incubated with isolated hepatocytes, indicating that reactive vinyl chloride metabolites formed by hepatocytes are stable enough to diffuse out of hepatocytes into sinusoidal cells. Glutathione added to the incubation medium inhibited the covalent protein binding of vinyl chloride metabolites in sinusoidal cells as wel…
Degradation of an alkaloid pheromone from the pale-brown chafer, Phyllopertha diversa (Coleoptera: Scarabaeidae), by an insect olfactory cytochrome P…
1999
AbstractThe pale-brown chafer, Phyllopertha diversa, utilizes an unusual alkaloid, 1,3-dimethyl-2,4-(1H,3H)-quinazolinedione, as its sex pheromone. This compound is rapidly degraded in vitro by the antennal protein extracts from this scarab beetle. Demethylation at the N-1 position and hydroxylation of the aromatic ring have been identified as the major catabolic pathways. The enzyme responsible for the pheromone degradation is membrane-bound, requires NAD(P)H for activity and is sensitive to cytochrome P450 inhibitors, such as proadifen and metyrapone. The ability to metabolize this unusual pheromone was not detected in 12 species tested, indicating that the P450 system, specific to male P…