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Study of serum levels of superoxide dismutase in preeclampsia and eclampsia: role of the test as a predictive tool.

AIM: To report serum levels of superoxide dismutase in women with preeclampsia and eclampsia. To document the use of the value as a predictive tool for deciding the time of onset of subsequent convulsions with fulminating eclampsia and use of the value as a marker for obstetric intervention in clinical severe preeclampsia and eclampsia. METHODS: Superoxide dismutase concentration was measured in a consecutive study in sera of women admitted in obstetric ward for preeclampsia and eclampsia, and compared with sera of normotensive, healthy pregnant women in third trimester. Three mL venous blood was subjected to superoxide dismutase estimation by pyrogallol autoxidation method. RESULTS: We found statistically significant difference (P < 0.05) in mean superoxide dismutase levels of normotensive pregnant women; and preeclamptic and eclamptic subjects, no statistically significant difference was found in between value of enzyme in preeclampsia and eclampsia (P > 0.05). Superoxide dismutase levels in two pregnancy outcomes; live births and still births, shows significant difference (P < 0.05), being 1.03 U/mL and 0.52 U/mL, respectively. The comparison of values before delivery and after delivery showed highly statistically significant difference (P < 0.001) in both groups separately. The cut-off value of serum superoxide dismutase 0.52 U/mL has sensitivity 68.5%, specificity 59.5% and negative predictive value of 78.6%, for predicting the fetal death as outcome of pregnancy with severe grade of disease. CONCLUSION: We found low levels of serum superoxide dismutase, less than 0.52 U/mL, being the predecessor of fulminating eclampsia. Our results support this predictive value of serum superoxide dismutase level as important in deciding the time of intervention as termination of pregnancy.

Adult↗

In vitro and in vivo effects of nitric oxide synthase inhibitors and nitric oxide inactivators on the South American opossum ileocolonic junction.

The potential role of nitrergic nerves in the regulation of the South American (SA) opossum ileocolonic junction (ICJ) function was investigated. In vitro, the effects of nitric oxide (NO) synthase inhibitors and NO inactivators on the non-adrenergic non-cholinergic (NANC) nerve-mediated relaxations of the circular muscle of the SA opossum ICJ were determined by employing isolated strips. Electrical field stimulation (0.2-8.0 Hz) caused frequency-dependent NANC relaxations. Nicotine and ATP also induced concentration dependent NANC relaxations that were abolished by tetrodotoxin (TTX). The relaxation response induced by NANC nerve activation was reduced in a dose dependent manner by NO synthase inhibitors while vasoactive intestinal peptide (VIP) and sodium nitroprusside (SNP) induced relaxations were uninfluenced by these drugs. In vivo, the NO synthase inhibitor, L-NAME, administered into the local artery caused a raise in intraluminal pressure of the ICJ in anaesthetized SA opossums in a L-arginine-preventable manner. Hydroquinone and pyrogallol, while being able to reduce, in a superoxide dimutase (SOD) reversible manner, the relaxations induced by exogenous NO failed to affect the NANC nerve-induced relaxations. Finally, neurones and nerve fibres in the myenteric plexus as well as varicose nerve fibres on the circular smooth layer were positive for NADPH-diaphorase activity. These findings indicate that nitrergic nerves inhibit ICJ circular smooth muscle in vitro and in vivo but cast doubts on the neuromediator being the NO radical.

Animals↗

Antisense suppression of l-galactose dehydrogenase in Arabidopsis thaliana provides evidence for its role in ascorbate synthesis and reveals light modulated l-galactose synthesis.

l-Galactose dehydrogenase (l-GalDH), a novel enzyme that oxidizes l-Gal to l-galactono-1,4-lactone (l-GalL), has been purified from pea seedlings and cloned from Arabidopsis thaliana. l-GalL is a proposed substrate for ascorbate biosynthesis in plants, therefore the function of l-GalDH in ascorbate biosynthesis was investigated by overexpression in tobacco and antisense suppression in A. thaliana. In tobacco the highest expressing lines had a 3.5-fold increase in extractable activity, but this did not increase leaf ascorbate concentration. Arabidopsis thaliana, transformed with an antisense l-GalDH construct, produced lines with 30% of wild-type activity. These had lower leaf ascorbate concentration when grown under high light conditions. l-Gal pool size increased in antisense transformants with low l-GalDH activity, and l-Gal concentration was negatively correlated with ascorbate. The results provide direct evidence for a role of l-GalDH in ascorbate biosynthesis. Ascorbate pool size in A. thaliana is increased by acclimation to high light, but l-GalDH expression was not affected. l-Gal accumulation was higher in antisense plants acclimated to high light, indicating that the capacity to synthesize l-Gal from GDP-mannose is increased. Because the only known function of l-GalL is ascorbate synthesis, these antisense plants provide an opportunity to investigate ascorbate function with minimal effects on carbohydrate metabolism. Measurements of other antioxidants revealed an increase in ascorbate- and pyrogallol-dependent peroxidase activity in low-ascorbate lines. As ascorbate is the major hydrogen peroxide-scavenging antioxidant in plants, this could indicate a compensatory mechanism for controlling hydrogen peroxide concentration.

Antioxidants↗

In vitro characterization of a plastid terminal oxidase (PTOX).

The plastid terminal oxidase (PTOX) encoded by the Arabidopsis IMMUTANS gene was expressed in Escherichia coli cells and its quinone/oxygen oxidoreductase activity monitored in isolated bacterial membranes using NADH as an electron donor. Specificity for plastoquinone was observed. Neither ubiquinone, duroquinone, phylloquinone nor benzoquinone could substitute for plastoquinone in this assay. However, duroquinol (fully reduced chemically) was an accepted substrate. Iron is also required and cannot be substituted by Cu(2+), Zn(2+) or Mn(2+). This plastoquinol oxidase activity is independent of temperature over the 15-40 degrees C range but increases with pH (from 5.5 to 9.0). Unlike higher plant mitochondrial alternative oxidases, to which PTOX shows sequence similarity (but also differences, especially in a putative quinone binding site and in cysteine conservation), PTOX activity does not appear to be regulated by pyruvate or any other tested sugar, nor by AMP. Its activity decreases, however, with increasing salt (NaCl or KCl) concentration. Various quinone analogues were tested for their inhibitory activity on PTOX. Pyrogallol analogues were found to be inhibitors, especially octyl gallate (I50 = 0.4 microM ) that appears far more potent than propyl gallate or gallic acid. Thus, octyl gallate is a useful inhibitor for future in vivo or in organello studies aimed at studying the roles of PTOX in chlororespiration and as a cofactor for carotenoid biosynthesis.

Amino Acid Sequence↗

A simple and efficient method for hemoglobin removal from mammalian tissue cytosol by zinc sulfate and its application to the study of lipoxygenase.

A simple and efficient method is described to remove hemoglobin (Hb) from human term placental cytosol to study dioxygenase and co-oxidase activities of lipoxygenase. In the untreated samples, 70%-80% of the linoleic acid-dependent dioxygenase and co-oxidase activities were found to be associated with the pseudo-lipoxygenase activity of Hb. Zinc sulfate (0.5 mM) precipitated >97% of the Hb present in the cytosol. The dioxygenase activity of the ZnSO4 treated cytosol exhibited a Vmax value of 313 nmoles linoleic acid hydroperoxide formed/min/mg protein and a K(M) of 1.4 mM for linoleic acid. The ZnSO4 treated cytosol displayed co-oxidase activity toward benzidine, dimethoxybenzidine, guaiacol, pyrogallol, tetramethylbenzidine and tetramethyl-p-phenylenediamine. Nordihydroguaiaretic acid, 5,8,11-eicosatriynoic acid, butylated hydroxyanisole, butylated hydroxytoluene and gossypol caused concentration dependent inhibition of dioxygenase and co-oxidase activities. These results suggest ZnSO4 precipitation of Hb from cytosol does not alter the functional characteristics of the human term placental lipoxygenase.

Chemical Precipitation↗

The effect of cyclic GMP on rabbit corporal smooth muscle tone and its modulation by cyclo-oxygenase products.

Corporal smooth muscle (CSM) tone is maintained by a finite balance between relaxant and contractile neurotransmitters. The aim of these experiments was to ascertain the degree to which cyclic GMP is involved in these interactions. We also sought to elucidate the pharmacological mechanism of action of MB in rabbit corpus cavernosum (RCC), an important tool in nitric oxide research. Using an organ chamber technique, strips of RCC were treated with the guanylate cyclase inhibitors Methylene Blue (MB) and LY83583; 100 microM MB led to increases in resting tension which were antagonized by indomethacin, nifedipine, phentolamine, but not superoxide dismutase (SOD). Contractile responses to noradrenaline (NA) were increased and relaxation to ACh was impaired by both MB and LY83583 and reversed with indomethacin, but not SOD. Pyrogallol had no effect on agonist-induced responses. The pharmacological action of MB in RCC does not depend on the generation of superoxide anions. Endothelium-dependent relaxation in RCC results in activation of soluble guanylate cyclase and release of a stable endothelium derived contracting factor(s), which is likely to be a constrictor prostanoid(s). Tonic production of cGMP in RCC inhibits the presynaptic release and contractile effects of NA and can be modulated by cyclo-oxygenase inhibition, demonstrating the important interaction and functional antagonism between cGMP and prostaglandins in the control of CSM tone.

Acetylcholine↗

Relaxant effects of flavonoids in isolated guinea pig trachea and their structure-activity relationships.

The structure-activity relationships between flavonoids and their tracheal relaxant action are little known. In the present study, 26 natural and synthetic flavonoids, divided into the five classes of flavones, flavonols, flavanones, isoflavones, and chalcones, were tested, and their IC (50) values were determined. The IC (50) values of these five classes indicated that flavones were more potent than flavonols. Flavones were also more potent than flavanones suggesting that the presence of a double bond between C-2 and C-3 is important. However, flavones were similar to isoflavones in potency. Chalcones, a class with an open C-ring, appeared to be the least potent among these five classes. Introduction of a hydroxy group at position C-6 of flavones increases their relaxant activities. So does adding a hydroxy group at position C-7 of flavones. It appears that the optimal number of hydroxy groups introduced to the A-ring of flavones is one. As more hydroxy groups are introduced to positions at C-5, C-6, and/or C-7 of flavones, the IC (50) values increase. It seems that flavones or flavonols with a pyrogallol moiety either in the A- or B-ring, respectively, have no activity. It appears that flavonols with ortho-hydroxy groups in the B-ring are more potent than those with meta-hydroxy groups. The activity of 6-hydroxyflavone disappears if the C-6 hydroxy group of the A-ring is methoxylated. If the C-4' hydroxy group of the B ring is methoxylated, the relaxant effect of these flavones is also attenuated or disappears. Therefore, the hydroxy group on either the A- or B-ring of flavones and flavonols being methylated resulted in lower potency of the tracheal relaxant effects. However, when all hydroxy groups on both the A- and B-rings of flavones or flavonols are methoxylated this results in higher potency. Therefore, the influence of methoxylation in flavones may be similar to that in flavonols. However, if the C-3 hydroxy group on the C-ring of flavonols, but not flavones which lack this hydroxy group, is methoxylated, the relaxant effects may increase. Glycosylation of the hydroxy group at position C-7 of flavones or flavanones attenuates the relaxant effects.

Animals↗

Trypanocidal effects of gallic acid and related compounds.

Gallic acid (3,4,5-trihydroxybenzoic acid) is a naturally abundant plant phenolic compound and it is well known as a component of hydrolyzable tannins. We report here that gallic acid and related compounds have trypanocidal activity against Trypanosoma brucei brucei (GUTat 3.1) in both the long slender bloodstream forms and the procyclic forms, in vitro. LD50 values of gallic acid are 46.96 +/- 1.28 microM for bloodstream forms and 30.02 +/- 3.49 for procyclic forms, respectively. A study of structurally related compounds suggested that the pyrogallol moiety could be responsible for this activity.

Animals↗

Organization of the interior of molecular capsules by hydrogen bonding.

The enclosure of functional entities within a protective boundary is an essential feature of biological systems. On a molecular scale, free-standing capsules with an internal volume sufficiently large to house molecular species have been synthesized and studied for more than a decade. These capsules have been prepared by either covalent synthesis or self-assembly, and the internal volumes have ranged from 200 to 1,500 A(3). Although biological systems possess a remarkable degree of order within the protective boundaries, to date only steric constraints have been used to order the guests within molecular capsules. In this article we describe the synthesis and characterization of hexameric molecular capsules held together by hydrogen bonding. These capsules possess internal order of the guests brought about by hydrogen bond donors within, but not used by, the framework of the capsule. The basic building blocks of the hexameric capsules are tetrameric macrocycles related to resorcin[4]arenes and pyrogallol[4]arenes. The former contain four 1,3-dihydroxybenzene rings bridged together by -CHR- units, whereas the latter contain four 1,2,3-trihydroxybenzene rings bridged together. We now report the synthesis of related mixed macrocycles, and the main focus is on the macrocycle composed of three 1,2,3-trihydroxybenzene rings and one 1,3-dihydroxybenzene ring bridged together. The mixed macrocycles self-assemble from a mixture of closely related compounds to form the hexameric capsule with internally ordered guests.

Benzene↗

Selective involvement of superoxide anion, but not downstream compounds hydrogen peroxide and peroxynitrite, in tumor necrosis factor-alpha-induced apoptosis of rat mesangial cells.

Tumor necrosis factor-alpha (TNF-alpha) induces reactive oxygen species (ROS) that serve as second messengers for intracellular signaling. Currently, precise roles of individual ROS in the actions of TNF-alpha remain to be elucidated. In this report, we investigated the roles of superoxide anion (O-(2)), hydrogen peroxide (H(2)O(2)), and peroxynitrite (ONOO(-)) in TNF-alpha-triggered apoptosis of mesangial cells. Mesangial cells stimulated by TNF-alpha produced O-(2) and underwent apoptosis. The apoptosis was inhibited by transfection with manganese superoxide dismutase or treatment with a pharmacological scavenger of O-(2), Tiron. In contrast, although exogenous H(2)O(2) induced apoptosis, TNF-alpha-triggered apoptosis was not affected either by transfection with catalase cDNA or by treatment with catalase protein or glutathione ethyl ester. Similarly, although ONOO(-) precursor SIN-1 induced apoptosis, treatment with a scavenger of ONOO(-), uric acid, or an inhibitor of nitric oxide synthesis, N(G)-nitro-L-argininemethyl ester hydrochloride, did not affect the TNF-alpha-triggered apoptosis. Like TNF-alpha-induced apoptosis, treatment with a O-(2)-releasing agent, pyrogallol, induced typical apoptosis even in the concurrent presence of scavengers for H(2)O(2) and ONOO(-). These results suggested that, in mesangial cells, TNF-alpha induces apoptosis through selective ROS. O-(2), but not H(2)O(2) or ONOO(-), was identified as the crucial mediator for the TNF-alpha-initiated, apoptotic pathway.

Animals↗

Total conversion of bifunctional catalase-peroxidase (KatG) to monofunctional peroxidase by exchange of a conserved distal side tyrosine.

Catalase-peroxidases (KatGs) are unique peroxidases exhibiting a high catalase activity and a peroxidase activity with a wide range of artificial electron donors. Exchange of tyrosine 249 in Synechocystis KatG, a distal side residue found in all as yet sequenced KatGs, had dramatic consequences on the bifunctional activity and the spectral features of the redox intermediate compound II. The Y249F variant lost catalase activity but retained a peroxidase activity (substrates o-dianisidine, pyrogallol, guaiacol, tyrosine, and ascorbate) similar to the wild-type protein. In contrast to wild-type KatG and similar to monofunctional peroxidases, the formation of the redox intermediate compound I could be followed spectroscopically even by addition of equimolar hydrogen peroxide to ferric Y249F. The corresponding bimolecular rate constant was determined to be (1.1 +/- 0.1) x 107 m-1 s-1 (pH 7 and 15 degrees C), which is typical for most peroxidases. Additionally, for the first time a clear transition of compound I to an oxoferryl-like compound II with peaks at 418, 530, and 558 nm was monitored when one-electron donors were added to compound I. Rate constants of reaction of compound I and compound II with tyrosine ((5.0 +/- 0.3) x 104 m-1 s-1 and (1.7 +/- 0.4) x 102 m-1 s-1) and ascorbate ((1.3 +/- 0.2) x 104 m-1 s-1 and (8.8 +/- 0.1) x 101 m-1 s-1 at pH 7 and 15 degrees C) were determined by using the sequential stopped-flow technique. The relevance of these findings is discussed with respect to the bifunctional activity of KatGs and the recently published first crystal structure.

Amino Acid Sequence↗

Intraocular pressure-lowering activity of phenolic antioxidants in normotensive rabbits.

PURPOSE: The purpose of this study was to determine the intraocular pressure (IOP)-lowering activity of phenolic antioxidants injected intravenously into normotensive rabbits. Antioxidants belonging to the following classes were tested: cinnamic acids; flavonols; flavanols; anthocyanidins; isoflavones; and tannic acid. METHODS: Test compounds were dissolved in either water or oil/saline as vehicle and injected intravenously into normotensive rabbits. IOP was monitored hourly after injection and expressed as a percent relative to preinjection values. Controls were conducted using vehicle alone. IOP from each eye was averaged to provide one value per rabbit. Dose-response data beginning at 0.01 mg-2 mg doses were collected for compounds shown to be active at 1 mg. RESULTS: Epigallocatechin, epigallocatechin gallate and myricetin lowered IOP below control levels at doses of 1 mg. Tannic acid was the most active, lowering IOP more than 30% at doses of 200 microg. CONCLUSION: Only phenolic antioxidants containing a pyrogallol B-ring system and nonaromatic C-ring (epigallocatechin, epigallocatechin gallate and myricetin) or possible galloyl glucosides as found in tannic acid were active in lowering IOP, with tannic acid being the most active. Other antioxidants were not active in this system suggesting a more specific structural requirement for interacting with appropriate ocular systems. The protein or proteoglycan-binding properties of these molecules may also be important in this activity.

Animals↗

The origin of urinary aromatic compounds excreted by ruminants. 3. The metabolism of phenolic compounds to simple phenols.

Dietary phenolic cinnamic acids are hydrogenated in the side-chain, demethylated and dehydroxylated in the rumen and are responsible for the large urinary output of benzoic acid by ruminants. 2. Decarboxylation of phenolic acids to simple phenols is another reaction of the intestinal microflora and experiments were made to determine the extent of this reaction in the rumen of sheep. 3. In five experiments phenolic compounds, quinic acid or casein were infused into the rumen or abomasum of sheep and increments in urinary outputs of phenolic acids and phenols determined by thin-layer and gas-liquid chromatography. 4. Production of phenols was almost exclusively confined to reactions in the rumen. 5. Rumen administration of phenolic benzoic or phenylacetic acids which contained a 4-hydroxy substituent yielded large increments in urinary phenol outputs. Other phenolic benzoic and phenylacetic acids were not decarboxylated. Rumen decarboxylation of 4-hydroxy-3-phenylpropionic acid did not occur and decarboxylation of 4-hydroxycinnamic acids was slight. 6. Nearly half the tyrosine content of rumen-administered casein was excreted as p-cresol, a decarboxylation product of 4-hydroxyphenylacetic acid, p-Cresol was the principal phenol found in sheep urine. 7. Catechol and phenol were consistently found in sheep urine samples and p-ethylphenol, resorcinol, quinol, 4-methylcatechol, orcinol and pyrogallol were also found when suitable precursors were infused to the rumen. 8. It is concluded that p-cresol is a rumen metabolite of tyrosine. The other phenols found are microbial metabolites of phenolic precursors which are either widely distributed in plants such as 4-hydroxybenzoic, protocatechuic and vanillic acids or of more limited distribution such as the orcinol glycosides of some Ericaceous plants.

Animals↗

In vitro solubility of uranium tetrafluoride with oxidizing medium compared with in vivo solubility in rats.

A simple in vitro solubility test for uranium tetrafluoride (UF4) was developed to investigate the effects of addition of enzymes, proteins or gases such as O2 to synthetic biological fluid or Gamble solvent. The tests were conducted concomitantly with an in vivo inhalation experiment using male rats. In the presence of Gamble solvent alone, UF4 exhibited class Y behaviour with a dissolution half-time of 300-500 days. However, when oxygen or carbonates were added to the Gamble solvent, UF4 displayed class W behaviour, with a half-time of 25-50 days. Lastly, in the presence of oxygen and pyrogallol, which simulates the action of the enzyme NADPH, the superoxide ion (O2-) was formed, which appears to have a dominant role in the oxidation of U4+ to U6+. Under these conditions UF4 behaved like a class D compound, and had a dissolution half-time of only 2-3 days. These latter results correlated with those of the inhalation experiment in which the dissolution half-time was calculated to be between 2.5 and 5.2 days. The data are also in agreement with urine monitoring data obtained for workers exposed to UF4 over a 20-year period.

Administration, Inhalation↗

Catalase-peroxidases in cyanobacteria--similarities and differences to ascorbate peroxidases.

Cyanobacteria (blue-green algae) are oxygenic phototrophic bacteria carrying out plant-type photosynthesis. The only hydrogen peroxide scavenging enzymes in at least two unicellular species have been demonstrated to be bifunctional cytosolic catalase-peroxidases (CatPXs) having considerable homology at the active site with plant ascorbate peroxidases (APXs). In this paper we examined optical and kinetic properties of CatPXs from the cyanobacteria Anacystis nidulans and Synechocystis PCC 6803 and discuss similarities and differences to plant APXs. Both CatPXs and APX showed similar spectra of the ferric enzyme, the redox intermediate Compound I and the cyanide complex, whereas the spectrum of CatPX Compound II had characteristics reminiscent of the spectrum of the native enzyme. Both steady-state and multi-mixing transient-state kinetic studies were performed in order to characterize the kinetic behaviour of CatPXs. Bimolecular rate constants of both formation and reduction of a CatPX Compound I are presented. Because of its intrinsic high catalase activity (which cannot be found in APXs), the rate constants for Compound I formation were measured with peroxoacetic acid and are shown to be 5.9 x 10(4) M(-1) s(-1) for CatPX from A. nidulans and 8.7 x 10(3) M(-1) s(-1) for the Synechocystis enzyme. Compared with o-dianisidine (2.7-6.7 x 10(6) M(-1) s(-1)) and pyrogallol (8.6 x 10(4)-1.6 x 10(5) M(-1) s(-1)), the rate constant for Compound I reduction by ascorbate was extremely low (5.4 x 10(3) M(-1) s(-1) at pH 7.0 and 15 degrees C), in marked contrast to the behaviour of APXs.

Ascorbate Peroxidases↗

Purification and characterization of polyphenol oxidase from nettle (Urtica dioica L.) and inhibitory effects of some chemicals on enzyme activity.

Polyphenol oxidase (PPO) of nettle (Urtica dioica L.) was extracted and purified through (NH4)2SO4 precipitation, dialysis, and CM-Sephadex ion-exchange chromatography and was used for its characterization. The PPO showed activity to catechol, 4-methylcatechol, L-3,4-dihydroxyphenylalanine (L-DOPA), L-tyrosine, p-cresol, pyrogallol, catechin and trans-cinnamic acid. For each of these eight substrates, optimum conditions such as pH and temperature were determined and L-tyrosine was found to be one of the most suitable substrates. Optimum pH and temperature were found at pH 4.5 and 30 degrees C respectively and Km and Vmax values were 7.90 x 10(-4) M, and 11290 EU/mL for with L-tyrosine as substrate. The inhibitory effect of several inhibitors, L-cysteine chloride, sodium azide, sodium cyanide, benzoic acid, salicylic acid, L-ascorbic acid, glutathione, thiourea, sodium diethyl dithiocarbamate, beta-mercaptoethanol and sodium metabisulfite were tested. The most effective was found to be sodium diethyl dithiocarbamate which acted as a competitive inhibitor with a Ki value of 1.79 x 10(-9)M. In addition one isoenzyme of PPO was detected by native polacrylamide slab gel electrophoresis.

Ascorbic Acid↗

Dimerization of ferulic and caffeic acids by purified peroxidase isolated from Bupleurum salicifolium callus culture.

A novel peroxidase that catalyses the transformation of caffeic acid and ferulic acid via oxidative coupling was purified from callus cultures of Bupleurum salicifolium petioles. The enzyme, which was purified over 2,900-fold, is a glycoprotein with a molecular weight of 38,000, determined by SDS/PAGE and gel filtration. The K(m) values obtained were 2.4x10(-4) M for caffeic and 2.6x10(-4) M for ferulic acid, while the K(m) values for H2O2 with caffeic acid was 4x10(-5) M and for H2O2 with ferulic acid was 4.8x10(-4) M. The purified peroxidase exhibits lower activity with typical peroxidase substrates (guaiacol and pyrogallol) than it does with caffeic and ferulic acids, but does not exhibit any activity with other phenylpropanoids tested (cinnamic acid, coumaric acid, and 3,4-dimethoxycinnamic acid).

Bupleurum↗

Comparison of the effects of 13 phenolic compounds in induction of proliferative lesions of the forestomach and increase in the labelling indices of the glandular stomach and urinary bladder epithelium of Syrian golden hamsters.

Groups of 6-week-old male Syrian golden hamsters were given 13 different phenolic compounds for 20 weeks. Of these compounds, 2(3)-tert-butyl-4-methoxyphenol (BHA), 2-tert-butyl-4-methylphenol (TBMP) and p-tert-butylphenol (PTBP) strongly induced hyperplasia and tumorous lesions in the forestomach. Catechol, p-methylphenol (PMYP), p-methoxyphenol (PMOP), caffeic acid, methylhydroquinone (MHQ) and pyrogallol were less active, and resorcinol, hydroquinone, propylparabene and tert-butylhydroquinone (TBHQ) were not active. The labelling index in the forestomach epithelium was significantly increased by addition to the diet of BHA, TBMP, catechol, PMOP, PTBP and MHQ. PMOP induced epithelial damage and regenerative hyperplasia of the pyloric region. Catechol, caffeic acid and PMYP induced similar though less marked lesions. The labelling index in the glandular stomach was significantly increased by oral catechol (P less than 0.05) or PMOP (P less than 0.05). No histopathological lesions were observed in the urinary bladder epithelium, but propylparabene (P less than 0.05), catechol, TBHQ and MHQ increased the labeling index. These findings indicate that PTBP and TBMP may be carcinogenic for hamster forestomach after long-term administration, and that both one hydroxy and tert-butyl substituents may be important for induction of hamster forestomach tumors.

Animals↗