Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “STILBENES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed1989

Lysine 539 of human band 3 is not essential for ion transport or inhibition by stilbene disulfonates.

The anion transporter from human red blood cells, band 3, has been expressed in Xenopus laevis frog oocytes microinjected with mRNA prepared from the cDNA clone. About 10% of the protein is present at the plasma membrane as determined by immunoprecipitation of covalently bound 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS) with anti-DIDS antibody. The expressed band 3 transport chloride at a rate comparable to that in erythrocytes. Transport of chloride is inhibited by stilbene disulfonates, niflumic acid, and dipyridamole at concentrations similar to those that inhibit transport in red blood cells: DIDS and 4,4'-dinitro-2,2'-stilbene disulfonate inhibit chloride uptake with Kiapp of 34 nM and 2.5 microM, respectively. Lysine 539 has been tentatively identified as the site of stilbene disulfonate binding. Site-directed mutagenesis of this lysine to five different amino acids has no effect on transport. Inhibition by stilbene disulfonates or their covalent binding was not affected when Lys-539 was substituted by Gln, Pro, Leu, or His. However, substitution by Ala resulted in weaker inhibition and covalent binding. These results indicate that lysine 539 is not part of the anion transport site and that it is not essential for stilbene disulfonate binding and inhibition.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1995

Stilbene disulfonic acids inhibit synexin-mediated membrane aggregation and fusion.

Stilbene disulfonic acids inhibit surfactant secretion from lung epithelial type II cells by an undefined mechanism, and inhibit CD4 mediated cell-cell fusion. We have previously shown that lung synexin promotes in vitro fusion of lamellar bodies and plasma membranes, an obligatory process for surfactant secretion. This study investigates the effect of stilbene disulfonic acids, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS), and 4-acetamido-4'-maleimidylstilbene-2,2'-disulfonic acid (AMDS), on synexin-mediated liposome aggregation and fusion. Structurally, these three stilbene compounds differ in the number of isothiocyano groups present (DIDS = 2, SITS = 1, and AMDS = 0). At 10 micrograms synexin/ml, DIDS and SITS inhibited synexin-mediated liposome aggregation with an EC50 of 3.5 microM and 148 microM, respectively. In comparison, AMDS was least inhibitory (EC50 > 1 mM). Thus, the inhibitory potency (DIDS > SITS > AMDS) was partly dependent upon the number of isothiocyano groups. The EC50 was also dependent on synexin concentration. Stilbene disulfonic acids were also inhibitory for arachidonic acid-enhanced synexin-mediated liposome fusion. The EC50 for DIDS and SITS for fusion were similar to that for liposome aggregation. Ca(2+)-induced synexin polymerization, measured by 90 degrees light scattering, was increased by DIDS, suggesting binding of stilbene disulfonic acids to synexin. The binding of DIDS to synexin was dependent on the molar ratio of synexin to DIDS. These results indicate that stilbene disulfonic acids interact directly with synexin to inhibit membrane aggregation and fusion. Our results suggest that such inhibition of synexin activity may contribute towards inhibition of surfactant secretion by DIDS, and support a physiological role for synexin in lung surfactant secretion.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMedDate not supplied

Grapevine protoplasts as a transient expression system for comparison of stilbene synthase genes containing cGMP-responsive promoter elements.

A method for preparing elicitor-responsive protoplasts from grapevine cells kept in suspension culture was established. The protoplasts were employed in order to perform transient gene expression experiments produced by externally added plasmids. Using the gene coding for bacterial beta-glucuronidase as the reporter gene, the transient expression under the control of various promoters of stilbene synthase genes were analyzed. The elicitor-responsiveness of promoters from grapevine genes and heterologous promoters were assayed: the grapevine stilbene synthase gene VST-1 and pine stilbene synthase genes PST-1, PST-2 and PST-3. Compared to the expression effected by the cauliflower mosaic virus 35S RNA-promoter, the stilbene synthase promoters caused a 2-5-fold increase in GUS-activity. Incubation of transformed protoplasts with fungal cell wall further stimulated the stilbene synthase promoters but not the 35S RNA-promoter. An even more pronounced differentiation between the promoters was observed when cGMP was included in the transient expression assays. Instead of treating transformed protoplasts with fungal cell wall we administered simultaneously cGMP and the plasmid to be tested. The cGMP-responsive increase was (a) specific concerning the nucleotide applied, (b) characteristic of grapevine protoplasts, and (c) not seen with shortened promoter-GUS constructs or GUS under the control of the 35S RNA-promoter. The highest cGMP-dependent response to stress was shown by the promoter of the grapevine stilbene synthase gene VST-1.

Acyltransferases↗
PubMed2004

Expression of the grapevine stilbene synthase gene VST1 in papaya provides increased resistance against diseases caused by Phytophthora palmivora.

The phytoalexin resveratrol (trans-3,5,4'-trihydroxy-stilbene), a natural component of resistance to fungal diseases in many plants, is synthesized by the enzyme trihydroxystilbene synthase (stilbene synthase, EC 2.3.1.95), which appears to be deficient or lacking in susceptible plants. Earlier workers isolated a stilbene synthase gene (Vst1) from grapevine (Vitis vinifera L.), which has subsequently been introduced as a transgene into a range of species to increase resistance of hosts to pathogens to which they were originally susceptible. Papaya (Carica papaya L.) is susceptible to a variety of fungal diseases, including root, stem, and fruit rot caused by the pathogen Phytophthora palmivora. Since resveratrol at 1.0 mM inhibited mycelium growth of P. palmivora in vitro, we hypothesized that papaya resistance to this pathogen might be increased by transformation with the grapevine stilbene synthase construct pVst1, containing the Vst1 gene and its pathogen-inducible promoter. Multiple transformed lines were produced, clonally propagated, and evaluated with a leaf disk bioassay and whole plant response to inoculation with P. palmivora. RNA transcripts of stilbene synthase and resveratrol glycoside were induced in plant lines transformed with the grapevine pVst1 construct shortly after pathogen inoculation, and the transformed papaya lines exhibited increased resistance to P. palmivora. The immature transformed plants appear normal and will be advanced to field trials to evaluate their utility.

Acyltransferases↗
PubMed1978

The effect of a disulfonic acid stilbene on proximal cell membrane potential in Necturus kidney.

The effects of 0.5 mM 4-acetamido-4'-isothiocyano-stilbene-2,2' disulfonic acid on the electrical properties of the peritubular membrane were studied in the proximal tubule of the perfused Necturus kidney. The addition of stilbene isothiocyanate disulfonic acid in peritubular perfusate resulted in an average 4.5 mV hyperpolarization with no detectable changes of peritubular membrane input conductance. The depolarization elicited by high-K media was enhanced by 18% in the presence of stilbene isothiocyanate disulfonic acid, an observation indicating that the inhibitor increased the contribution of potassium to membrane potential, presumably by decreasing anionic permeabilities. The hyperpolarizing effect of stilbene isothiocyanate disulfonic acid was abolished when peritubular bicarbonate was removed from the medium and isoosmotically replaced by chloride. These data suggest that (a) intracellular bicarbonate activity is higher than that predicted from passive distribution, (b) stilbene isothiocyanate disulfonic acid decreases P HCO3, thus hyperpolarizing the membrane, (c) chloride distribution appears to be passive when bicarbonate is removed from the peritubular perfusate. The state of Cl distribution when extracellular bicarbonate is at physiologic concentration cannot be assessed from the present data.

Animals↗
PubMed1982

The effect of trans-stilbene oxide and other structurally related inducers of drug-metabolizing enzymes on the pentose phosphate pathway and other enzymes of carbohydrate metabolism.

trans-Stilbene oxide has been found earlier to be a new type of inducer of drug-metabolizing systems. Here we demonstrate that treatment of rats with this xenobiotic results in an increase in the activity of the cytosolic glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, the first and third enzymes in th pentose phosphate pathway, to 350% and 170% of the control values, respectively. At the time microsomal glucose 6-phosphate dehydrogenase activity was unaffected by administration of trans-stilbene oxide or benzil. The time course and dose-response of the increases in glucose 6-phosphate and 6-phosphogluconate dehydrogenase activities have been characterized. The activities of ribulose 5-phosphate 3-epimerase and ribose 5-phosphate activities have been characterized. The activities of ribulose 5-phosphate 3-epimerase and ribose 5-phosphate ketol isomerase, enzymes further along in the pentose phosphate pathway, were not significantly affected by trans-stilbene oxide or benzil. An investigation of the effect of treating rats with different metabolites of stilbene and with other structurally related compounds on hepatic cytosolic glucose 6-phosphate dehydrogenase activity revealed the structural features which are important for increasing this activity. Finally, it was found that administration of trans-stilbene oxide did not affect the activities of glucokinase and phosphoglucose isomerase, the two glycolytic enzymes which can produce glucose 6-phosphate, the link between glycolysis and the pentose phosphate shunt.

Animals↗
PubMed1984

Purification and characterization of the major microsomal cytochrome P-450 form induced by trans-stilbene oxide in rat liver.

The major form of microsomal cytochrome P-450 induced by trans-stilbene oxide in the liver of male Sprague-Dawley rats was purified and characterized, and compared with the isolated cytochrome P-450 B2 forms from phenobarbital- and 3-methylcholanthrene-pretreated animals. The apparent subunit molecular weight of the trans-stilbene oxide-induced cytochrome was found to be 53 000 using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the absorbance maximum of the carbon monoxide complex of the ferrous cytochrome was 450 nm. Reconstitution of the N-demethylase activity towards three different substrates showed high and similar activities with the cytochrome P-450 B2 forms from trans-stilbene oxide or phenobarbital-treated rats, with one exception. Amino-acid analysis also showed a very high degree of similarity between these two forms. Upon proteinase treatment with three different proteinases the trans-stilbene oxide-induced cytochrome demonstrated in each case a peptide pattern identical to that obtained with the phenobarbital-induced B2 form. Furthermore, both forms are completely immunologically cross-reactive. We therefore conclude from these experiments that the liver microsomal P-450 B2 from trans-stilbene oxide and phenobarbital-treated rats are very closely related, if not identical.

Amino Acids↗
PubMed2003

Pharmacological inhibition of outwardly rectifying Cl- currents in rat peritoneal mast cells: a comparison of different stilbene derivatives.

Diethylstilbestrol and other stilbene derivatives can provide some inhibition of the outwardly rectifying Cl- current (I(Cl-,OR)) in rat peritoneal mast cells. In order to elucidate structure-activity relationships of diethylstilbestrol, 12 stilbenes as well as 17beta-estradiol and hexestrol were tested in rat peritoneal mast cells using the nystatin-perforated patch approach of the whole-cell patch-clamp technique. Since trans-stilbene showed no effect, the substituents of diethylstilbestrol must be of importance. The introduction of only one hydroxy group in trans-stilbene produced potent inhibition of the I(Cl-,OR) (IC50: 3.3 microM). But in contrast, resveratrol with hydroxy groups at positions 4, 3', and 5' as well as methoxy substituted stilbene derivatives and 17beta-estradiol were ineffective. On the other hand, hexestrol potently inhibited I(Cl-,OR) indicating that the aromatic ring systems can also be connected by an ethyl bridge. In summary, a hydroxy group at position 4 (or 4') is a prerequisite for diethylstilbestrol-mediated inhibition of I(Cl-,OR).

Animals↗
PubMed2005

F-18 Polyethyleneglycol stilbenes as PET imaging agents targeting Abeta aggregates in the brain.

This paper describes a novel series of 18F-labeled polyethyleneglycol (PEG)-stilbene derivatives as potential beta-amyloid (Abeta) plaque-specific imaging agents for positron emission tomography (PET). In these series of compounds, 18F is linked to the stilbene through a PEG chain, of which the number of ethoxy groups ranges from 2 to 5. The purpose of adding PEG groups is to lower the lipophilicity and improve bioavailability. The syntheses of the "cold" compounds and the 18F-labeled PEG stilbene derivatives are successfully achieved. All of the fluorinated stilbenes displayed high binding affinities in an assay using postmortem AD brain homogenates (K(i)=2.9-6.7 nM). Labeling was successfully performed by a substitution of the mesylate group of 10a-d by [18F]fluoride giving the target compounds [18F]12a-d (EOS, specific activity, 900-1500 Ci/mmol; radiochemical purity >99%). In vivo biodistribution of these novel (18)F ligands in normal mice exhibited excellent brain penetrations and rapid washouts after an intravenous injection (6.6-8.1 and 1.2-2.6 %dose/g at 2 and 60 min, respectively). Autoradiography of postmortem AD brain sections of [18F]12a-d confirmed the specific binding related to the presence of Abeta plaques. In addition, in vivo plaque labeling can be clearly demonstrated with these 18F-labeled agents in transgenic mice (Tg2576), a useful animal model for Alzheimer's disease. In conclusion, the preliminary results strongly suggest these fluorinated PEG stilbene derivatives are suitable candidates as Abeta plaque imaging agents for studying patients with Alzheimer's disease.

Alzheimer Disease↗
PubMed2003

Aromatic and pyrone polyketides synthesized by a stilbene synthase from Rheum tataricum.

A cDNA encoding a stilbene synthase, RtSTS, was isolated from the rhizomes of Tatar rhubarb, Rheum tataricum L. (Polygonaceae), a medicinal plant containing stilbenes and other polyketides. Recombinant RtSTS was expressed in E. coli and assayed with acetyl-coenzyme A (CoA), n-butyryl-CoA, isovaleryl-CoA, n-hexanoyl-CoA, cinnamoyl-CoA and p-coumaroyl-CoA as primers of polyketide synthesis. RtSTS synthesized resveratrol and a trace amount of naringenin chalcone from p-coumaroyl-CoA, supporting the enzyme's identification as a resveratrol-type stilbene synthase (EC 2.3.1.95). Bis-noryangonin and p-coumaroyl triacetic acid lactone (CTAL)-type pyrones were observed in minor amounts in the reaction with p-coumaroyl-CoA and as major products with cinnamoyl CoA. As well, such pyrones, and not aromatic polyketides, were identified as the only products in assays with aliphatic and benzoyl CoA esters. Acetonyl-4-hydroxy-2-pyrone, a pyrone synthesized from acetyl-CoA, was identified as a new product of a stilbene synthase. Using Northern blot analysis, RtSTS transcript was found to be highly expressed in R. tataricum rhizomes, with low transcript levels also present in young leaves. This expression pattern correlated with the occurrence of resveratrol, which was detected in higher amounts in R. tataricum rhizomes compared with leaves and petioles using HPLC. Few stilbene synthases have been found in plants, and the identification of RtSTS provides additional sequence and catalytic information with which to study the evolution of plant polyketide synthases.

Acyl Coenzyme A↗
PubMed2002

Synthesis, structure, and photochemistry of exceptionally stable synthetic DNA hairpins with stilbene diether linkers.

The structure and properties of 18 hairpin-forming bis(oligonucleotide) conjugates possessing stilbene diether linkers are reported. Conjugates possessing bis(2-hydroxyethyl)stilbene 4,4'-diether linkers form the most stable DNA hairpins reported to date. Hairpins with as few as two T:A base pairs or four noncanonical G:G base pairs are stable at room temperature. Increasing the length of the hydroxyalkyl groups results in a decrease in hairpin thermal stability. On the basis of the investigation of their circular dichroism spectra, all of the hairpins investigated adopt B-DNA structures, except for a hairpin with a short poly(G:C) stem which forms a Z-DNA structure. Both the strong fluorescence of the stilbene diether linkers and their trans-cis photoisomerization are totally quenched in hairpins possessing neighboring T:A and G:C base pairs. Quenching is attributed to an electron-transfer mechanism in which the singlet stilbene serves as an electron donor and T or C serves as an electron acceptor. In contrast, in denatured hairpins and hairpins possessing neighboring G:G base pairs the stilbene diether linkers undergo efficient photoisomerization.

Circular Dichroism↗
PubMed2002

Postharvest stilbene-enrichment of red and white table grape varieties using UV-C irradiation pulses.

The red table grape varieties Flame, Red Globe, Crimson, and Napoleon, as well as the white varieties Superior, Dominga, and Moscatel Italica, were irradiated with a previously optimized UV-C postharvest irradiation protocol (510 W, 40 cm, 60 s). The induction kinetics of the stilbenes trans-resveratrol, trans-piceid, trans-piceatannol, trans-astringin, and viniferins was followed by using HPLC-DAD/MS/MS. The most inducible stilbenes were trans-resveratrol, trans-piceatannol, and viniferins. Both quantitative and qualitative differences were observed in both the stilbene induction kinetics and stilbene content in the seven table grapes analyzed here. The total resveratrol content ranged from 0.69 mg/100 g fw (Dominga) to 2.3 mg/100 g fw (Red Globe). The net resveratrol induction ranged from 3.4-fold (Flame) to 2315-fold (Red Globe). The highest viniferins content was observed in the variety Flame (0.73 mg/100 g fw), although the variety Red Globe presented the highest viniferins induction (175-fold). The highest content and induction of piceatannol (0.17 mg/100 g fw and 173-fold, respectively) was observed in the variety Flame. It should be stressed that taking into account the health-beneficial effects claimed for stilbenes, the UV-C irradiated table grapes can be considered as new functional fruits that can supply (a serving of unpeeled 200 g table grapes) the resveratrol content (depending on the variety) equivalent to more than seven glasses of red wine ( approximately 1.5 L) with high resveratrol content.

Chromatography, High Pressure Liquid↗
PubMed2003

Postharvest UV-C-irradiated grapes as a potential source for producing stilbene-enriched red wines.

The use of postharvest controlled irradiation by UV pulses is proposed as a potential method to produce stilbene-enriched red wine. "Monastrell" grapes were UV-C-irradiated to increase stilbene content. The main inducible stilbenes were resveratrol and piceatannol, which are molecules with reported health-beneficial activities. The evolution of both compounds was followed in the different steps of an "analytical" traditional maceration wine-making process. The final wine made from UV-C-irradiated grapes was enriched about 2- and 1.5-fold in resveratrol and piceatannol, respectively, when compared to the control wine. In addition, no difference was detected regarding the standard enological parameters (color, acidity, etc.). It is strongly suggested that, with the use of more susceptible wine grapes to induce bioactive stilbenes upon UV-C irradiation, the stilbene-enrichment of wine can be much higher.

Chromatography, High Pressure Liquid↗
PubMed2006

Antioxidant effects and hepatoprotective activity of 2,5-dihydroxy-4,3'-di(beta-d-glucopyranosyloxy)-trans-stilbene from Morus bombycis Koidzumi roots on CCl4-induced liver damage.

We investigated hepatoprotective activity and antioxidant effect of the 2,5-dihydroxy-4,3'-di(beta-D-glucopyranosyloxy)-trans-stilbene that purified from Morus bombycis Koidzumi roots against CCl4-induced liver damage in rats. The 2,5-dihydroxy-4,3'-di(beta-D-glucopyranosyloxy)-trans-stilbene displayed dose-dependent superoxide radical scavenging activity (IC50 = 430.2 microg/ml), as assayed by the electron spin resonance (ESR) spin-trapping technique. The increase in aspartate aminotransferase (AST) activities in serum associated with carbon tetrachloride (CCl4)-induced liver injury was inhibited by 2,5-dihydroxy-4,3'-di(beta-D-glucopyranosyloxy)-trans-stilbene and at a dose of 400 - 600 mg/kg samples had hepatoprotective activity comparable to the standard agent, silymarin. The biochemical assays were confirmed by histological observations showing that the 2,5-dihydroxy-4,3'-di(beta-d-glucopyranosyloxy)-trans-stilbene decreased cell ballooning in response to CCl4 treatment. These results demonstrate that the 2,5-dihydroxy-4,3'-di(beta-D-glucopyranosyloxy)-trans-stilbene is a potent antioxidant with a liver protective action against CCl4-induced hepatotoxicity.

Animals↗
PubMed2000

Reductive metabolism of stilbene oxide and styrene oxide to the olefins in rats.

The present study provides the first evidence that stilbene oxide and styrene oxide are reductively metabolized to the corresponding olefins in rats. When cis- or trans-stilbene oxide was given orally to rats, both cis- and trans-stilbene were isolated from the urine and feces. Styrene was also isolated from the urine and feces of rats given styrene oxide. These metabolites were identified unequivocally by UV and mass spectral comparison with authentic samples, and on the basis of their TLC and HPLC behavior. However, these olefins were not detected in the urine or feces of antibiotics-treated rats dosed with cis- or trans-stilbene oxide. Cecal contents of the untreated rats exhibited olefin oxide reductase activities toward cis- and trans-stilbene oxides under anaerobic conditions. The results suggest that intestinal bacteria play an important role in the reduction of olefin oxides to the corresponding olefins in the animal body.

Alkenes↗
PubMed2003

Comparative molecular field analysis study of stilbene derivatives active against A549 lung carcinoma.

A series of 43 stilbene derivatives that showed cytotoxicity against human lung carcinoma (A549) was analyzed using comparative molecular field analysis (CoMFA) for defining the hypothetic pharmacophore model. The polyoxylated stilbenes were found to be active inhibitors of tubulin polymerization. Several cis-stilbenes are structurally similar to combretastatins. However, the trans-stilbenes are assumed to be close to resveratrol found in grapes and have been reported to be potential cancer chemopreventive agents by modulating the initiation, promotion, and progression of the carcinogenic process. With several synthesized compounds that were evaluated for antitumor cytotoxicity against human lung tumor cells (A549), the stilbene derivatives were subjected to CoMFA. To perform systematic molecular modeling of these compounds, a conformational search was carried out based on the precise dihedral angle analysis of the lead compound (1p). The X-ray crystallographic structure of combretastatin A-1 was also used for defining the active conformers of the compounds. After determining the energy-minimized conformers of the lead compound (1p), CoMFA was performed using five different alignments. The three dimensional (3D)-quantitative structure-activity relationship study resulted in reasonable cross-validated, conventional r(2) values equal to 0.640 and 0.958, respectively.

Algorithms↗
PubMed1999

Stilbene compounds: from the grapevine to wine.

Stilbenes are natural compounds occurring in a number of plant families, including Vitaceae and (within this family) Vitis vinifera L., which is the most important species grown worldwide for grape and wine production. Stilbenes (resveratrol and viniferins) are present in grapevine as constitutive compounds of the woody organs (roots, canes, stems) and as induced substances (in leaves and fruit) acting as phytoalexins in the mechanisms of grape resistance against certain pathogens. Resveratrol (3, 5, 4'-trihydroxystilbene) was also detected in wine and it was thought to be the active principle of red wines that were shown to reduce heart diseases. This paper reviews data, obtained by the Viticulture Institute of the Catholic University at Piacenza and taken from the literature, on some aspects of stilbene physiology in grapevine and on their relation to resveratrol wine levels. Constitutive stilbene contents of woody organs are reported, as well as the possible role of cluster stems as a source of resveratrol for wine. The accumulation of stilbenes in grape berries infected by grey mould (Botrytis cinerea Pers.) has been investigated and the effects of environmental factors on resveratrol grape and wine levels will be discussed. An unidentified new hydroxystilbene was detected in wine.

Anti-Infective Agents↗
PubMed1983

Effects of phenobarbital, trans-stilbene oxide, and 3-methylcholanthrene on epoxide hydrolase within centrilobular, midzonal, and periportal regions of rat liver.

The effects of phenobarbital, trans-stilbene oxide, and 3-methylcholanthrene on epoxide hydrolase (EC 3.3.2.3) within centrilobular, midzonal, and periportal hepatocytes were investigated employing rabbit anti-serum produced against rat hepatic microsomal epoxide hydrolase in unlabeled antibody peroxidase-anti-peroxidase and indirect fluorescent antibody-staining techniques. In livers of control rats, midzonal and periportal hepatocytes bound the anti-epoxide hydrolase to similar extents while centrilobular hepatocytes bound approximately 25% more antibody. 3-Methylcholanthrene did not cause significant alterations in immunohistochemical staining for epoxide hydrolase within any region of the liver lobule, whereas phenobarbital and trans-stilbene oxide produced significant alterations in both the intensity and pattern of intralobular staining for the enzyme. After 4 days of phenobarbital pretreatment, anti-epoxide hydrolase binding to hepatocytes was slightly, but significantly, elevated, especially within midzonal regions. After 7 days of phenobarbital pretreatment, anti-epoxide hydrolase binding was increased by approximately 65% within midzonal regions and by approximately 41 and 24%, respectively, within centrilobular and periportal regions. In livers of trans-stilbene oxide-pretreated rats, anti-epoxide hydrolase binding was increased by approximately 80% within both the midzonal and periportal regions and by approximately 43% within centrilobular regions. These immunohistochemical findings demonstrate that phenobarbital and trans-stilbene oxide both induce epoxide hydrolase nonuniformly within the liver lobule. However, while phenobarbital induces the enzyme to the greatest extent within midzonal hepatocytes and to the least extent within periportal hepatocytes, trans-stilbene oxide induces epoxide hydrolase equally within midzonal and periportal hepatocytes.

Animals↗