Search results for "Microsoma"
showing 10 items of 78 documents
Xenobiotic metabolizing enzymes of rat liver nonparenchymal cells.
1986
Abstract The nonparenchymal cells (NPC) of the liver are primarily located along the sinusoids and therefore are the first cells to encounter blood-borne xenobiotics. To study the possible role of the NPC in the metabolism of xenobiotics, populations of NPC and parenchymal cells (PC) were prepared from rats and various xenobiotic metabolizing enzyme activities investigated. The specific activity of every enzyme studied (ethoxyresorufin deethylase, benzphetamine demethylase, glutathione transferase, UDP glucuronosyltransferase, and microsomal epoxide hydrolase) was 12 to 1000% higher in the PC than in the NPC populations and the patterns of activities between the two populations were remarka…
Time-dependence and differential induction of rat and guinea pig peroxisomal beta-oxidation, palmitoyl-CoA hydrolase, cytosolic and microsomal epoxid…
1988
Fischer-344 rats and Hartley guinea pigs received a diet containing 0.01% (w/w), 0.05% (w/w), or 0.25% (w/w) of the hypolipidemic drug fenofibrate. Rats were treated for 4, 7, 14, or 21 days, and a clear dose-dependent and weak time-dependent increase in liver/body weight ratio was observed. The specific activity of peroxisomal beta-oxidation increased linearly with time at all concentrations used. A dose-dependent increase in cEH was observed, but the activity remained constant after treatment for 7 days. Enhancement of palmitoyl-CoA hydrolase was dose-dependent, but was similar at all 4 time points investigated. In contrast to the other enzyme activities, mEH was not or only minimally (le…
Properties of the microsomal and cytosolic glutathione transferases involved in hexachloro-1:3-butadiene conjugation
1989
Hexachloro-1,3-butadiene (HCBD) is a substrate for the hepatic microsomal glutathione transferases and is metabolised at higher rates by these enzymes than their cytosolic counterparts. Conjugation reactions catalysed by the microsomal and cytosolic transferases have been studied and characterized using this substrate and 1-chloro-2,4-dinitrobenzene (CDNB). In rat liver microsomes the Km values for HCBD and CDNB were 0.91 and 0.012 mM and in cytosol 0.51 and 0.10 mM respectively. Vmax values for HCBD were 1.39 and 0.35 nmol conjugate formed/min/mg protein for microsomes and cytosol respectively. In microsomal systems HCBD was a potent competitive inhibitor of the metabolism of CDNB with a K…
Visualization of a covalent intermediate between microsomal epoxide hydrolase, but not cholesterol epoxide hydrolase, and their substrates
1997
Mammalian soluble and microsomal epoxide hydrolases have been proposed to belong to the family of alpha/beta-hydrolase-fold enzymes. These enzymes hydrolyse their substrates by a catalytic triad, with the first step of the enzymatic reaction being the formation of a covalent enzyme-substrate ester. In the present paper, we describe the direct visualization of the ester formation between rat microsomal epoxide hydrolase and its substrate. Microsomal epoxide hydrolase was precipitated with acetone after brief incubation with [1-(14)C]epoxystearic acid. After denaturing SDS gel electrophoresis the protein-bound radioactivity was detected by fluorography. Pure epoxide hydrolase and crude micros…
Induction of rat liver microsomal epoxide hydrolase by its endogenous substrate 16α, 17α-epoxyestra-1,3,5-trien-3-ol
1995
1. The influence of the endogenous steroid epoxides 16 alpha, 17 alpha-epoxyestra-1,3,5(10)-trien-3-ol (estroxide) and 16 alpha, 17 alpha-expoxiandrost-4-en-3-one (androstene oxide) and their metabolic precursors estra-1,3,5(10), 16-tetraen-3-ol (estratetraenol) and androsta-4, 16-dien-3-one (androstadienone) on the specific activities of hepatic microsomal and soluble epoxide hydrolase, glutathione S-transferase, dihydrodiol dehydrogenase, and 7-ethoxycoumarin deethylase was investigated in the male Sprague-Dawley rat. 2. Both estroxide and estratetraenol induced microsomal epoxide hydrolase activity towards styrene oxide and estroxide itself 2-2.5-fold and glutathione conjugation of 1-chl…
Purification and characterization of rat-liver cytosolic epoxide hydrolase.
1988
Rat liver cytosolic epoxide hydrolase has been purified and characterized. The enzyme was purified from tiadenol-induced rat liver 540-fold with respect to trans-stilbene oxide as a substrate. Similar purification was obtained with the substrates trans-beta-ethyl styrene oxide and styrene 7,8-oxide, the specific activities decreasing in the order trans-beta-ethyl styrene oxide greater than styrene 7,8-oxide greater than trans-stilbene oxide. The enzyme exerts highest activity at pH 7.4 Km and Vmax of the pure enzyme for trans-stilbene oxide were 1.7 microM and 205 nmol x min-1 x mg protein-1 respectively. With trans-stilbene oxide as a substrate, the inhibition by organic solvents (2.5% by …
Metabolism of coumarin by precision-cut calf liver slices and calf liver microsomes.
1995
1. The metabolism of 50 microM [3-14C]coumarin has been studied in precision-cut-calf liver slices. 2. The metabolism of 50 microM coumarin to 7-hydroxycoumarin has also been examined in calf, rat, Cynomolgus monkey and human liver microsomal preparations. 3. In precision-cut calf liver slices, [3-14C]coumarin was metabolized to various polar products and to metabolite(s) that bound covalently to calf liver slice proteins. The polar products included 7-hydroxycoumarin (which was extensively conjugated with D-glucuronic acid and/or sulphate), metabolites of the 3-hydroxylation pathway (mainly o-hydroxyphenylethanol and o-hydroxyphenylacetic acid), and unknown metabolites. 4. Coumarin 7-hydro…
cis- and trans-1,2-diphenylaziridines: induction of xenobiotic-metabolizing enzymes in rat liver and mutagenicity in Salmonella typhimurium.
1986
trans-Stilbene imine (trans-1,2-diphenylaziridine) is the nitrogen analog of trans-stilbene oxide, a potent inducer of several microsomal and cytosolic xenobiotic-metabolizing enzymes. Although the acute toxicity of cis- and trans-stilbene imines prevents their application at the usual dose for trans-stilbene oxide (400 mg/kg/day), it is apparent that the imines nevertheless potently induce several xenobiotic-metabolizing enzymes in rat liver. The IP administration of trans-stilbene imine resulted in statistically significant increases in the activities of aminopyrine N-demethylase, microsomal epoxide hydrolase, glutathione transferase (toward 1-chloro-2,4-dinitrobenzene, 1,2-dichloro-4-nit…
Microsomal Biotransformation of Benzo[ghi]perylene, a Mutagenic Polycyclic Aromatic Hydrocarbon without a “Classic” Bay Region
2005
Carcinogenic polycyclic aromatic hydrocarbons (PAH), e.g., benzo[a]pyrene (BaP), possess a bay region comprising an ortho-fused benzene ring. Benzo[ghi]perylene (BghiP) represents the group of PAHs lacking such a "classic" bay region and hence cannot be metabolically converted like BaP to bay region dihydrodiol epoxides considered as ultimate mutagenic and carcinogenic metabolites of PAH. BghiP exhibits bacterial mutagenicity in strains TA98 (1.3 his(+)-revertant colonies/nmol) and TA100 (4.3 his(+)-revertant colonies/nmol) of Salmonella typhimurium after metabolic activation by the postmitochondrial hepatic fraction of CD rats treated with 3-methylcholanthrene. Inhibition of microsomal epo…
Biphenyl and fluorinated derivatives: liver enzyme-mediated mutagenicity detected in Salmonella typhimurium and Chinese hamster V79 cells.
1992
Abstract Hepatocarcinogenic polychlorinated and polybrominated biphenyls usually show negative results in in vitro mutagenicity assays. Problems in their testing result from their low water solubility and their slow rate of metabolism. We therefore investigated better soluble model compounds, namely biphenyl and its 3 possible monofiuorinated derivatives. In the direct test, these compounds proved tobe nonmutagenic in Salmonella typhimurium TA98 and TA100 (reversion to histidine prototrophy) and in Chinese hamster V79 cells (acquisition of resistance to 6-thioguanine). However, when the exposure was carried out in the presence of NADPH-fortified postmitochondrial fraction of liver homogenat…