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PubMedDate not supplied

Cytotoxicity and radical intensity of eugenol, isoeugenol or related dimers.

To investigate the possible link between radicals and cytotoxicity of eugenol-related compounds, dimer compounds were synthesized from eugenol (4-allyl-2-methoxyphenol) or isoeugenol (4-propenyl-2-methoxyphenol): bis-eugenol (3,3'-dimethoxy-5,5'-di-2-propenyl-1,1'-biphenyl-2,2'-diol); dehydrodiisoeugenol (2-(3-methoxy-4-hydroxyphenyl)-3-methyl-5-(1-propenyl)-7-methoxy-2,3- dihydrobenzofuran) and alpha-di-isoeugenol (r-l-ethyl-5-hydroxy-t-3-(4-hydroxy-3-methoxyphenyl)-6-methoxy-c-2- methylindane). Both the cytotoxic activity and the DNA synthesis inhibitory activity of these compounds against a salivary gland tumor cell line (HSG) and normal human gingival fibroblast (HGF) were decreased in the order of: dehydrodiisoeugenol, alpha-di-isoeugenol > isoeugenol > eugenol > bis-eugenol. Electron spin resonance (ESR) spectroscopy showed that dehydrodiisoeugenol, alpha-di-isoeugenol and eugenol, but not isoeugenol and bis-eugenol, produced phenoxyl radicals under alkaline condition (pH > 9.5). However, benzyl radicals were produced during the dimerization of isoeugenol to dehydrodiisoeugenol. The radical intensity of alpha-di- and dehydrodiisoeugenol appeared at relatively later incubation time than eugenol, suggesting that their phenoxyl radical was more stable than that of eugenol. Such a phenoxyl radical is produced by scavenging free radicals, during the inhibition of lipid peroxidation. Higher cytotoxic activity of isoeugenol dimers was thought to be induced by interaction with cell membranes via the lipophilic radical. The present study supports the notion that relative cytotoxicity of chemicals can be evaluated by measuring the radical intensity using ESR.

Antineoplastic Agents↗
PubMedDate not supplied

Effect of antioxidants on radical intensity and cytotoxic activity of eugenol.

The effect of antioxidants on the radical intensity of 2-methoxy-4-(2-propenyl)phenol (eugenol) was investigated, using ESR spectroscopy. Eugenol produced radicals in alkaline solutions, with an optimum pH of 9.5. The intensity of eugenol radical was a positive function of its concentration, reaching a plateau level at 100 mM. The eugenol radical was rapidly diminished under alkaline conditions. Water-soluble antioxidants, such as cysteine, N-acetyl-L-cysteine, glutathione and sodium ascorbate, completely scavenged the eugenol radical. Gallic acid at lower doses significantly, but not completely, scavenged the eugenol radical. Among water-insoluble antioxidants, terpenes (beta-carotene, retinol, lycopene) effectively scavenged the eugenol radical, whereas phenolic compounds (alpha-tocopherol, Trolox) were inactive. Millimolar concentrations of eugenol were cytotoxic against human salivary gland and oral squamous carcinoma cell lines. Addition of sodium ascorbate or beta-carotene reproducibly reduced the cytotoxic activity of eugenol. The applicability of the antioxidants in dentistry was discussed.

Acetylcysteine↗
PubMed2000

Biosynthesis of estragole and methyl-eugenol in sweet basil (Ocimum basilicum L). Developmental and chemotypic association of allylphenol O-methyltransferase activities.

Sweet basil (Ocimum basilicum L., Lamiaceae) is a common herb, used for culinary and medicinal purposes. The essential oils of different sweet basil chemotypes contain various proportions of the allyl phenol derivatives estragole (methyl chavicol), eugenol, and methyl eugenol, as well as the monoterpene alcohol linalool. To monitor the developmental regulation of estragole biosynthesis in sweet basil, an enzymatic assay for S-adenosyl-L-methionine (SAM):chavicol O-methyltransferase activity was developed. Young leaves display high levels of chavicol O-methyltransferase activity, but the activity was negligible in older leaves, indicating that the O-methylation of chavicol primarily occurs early during leaf development. The O-methyltransferase activities detected in different sweet basil genotypes differed in their substrate specificities towards the methyl acceptor substrate. In the high-estragole-containing chemotype R3, the O-methyltransferase activity was highly specific for chavicol, while eugenol was virtually not O-methylated. In contrast, chemotype 147/97, that contains equal levels of estragole and methyl eugenol, displayed O-methyltransferase activities that accepted both chavicol and eugenol as substrates, generating estragole and methyl eugenol, respectively. Chemotype SW that contains high levels of eugenol, but lacks both estragole and methyl eugenol, had apparently no allylphenol dependent O-methyltransferase activities. These results indicate the presence of at least two types of allylphenol-specific O-methyltransferase activities in sweet basil chemotypes, one highly specific for chavicol; and a different one that can accept eugenol as a substrate. The relative availability and substrate specificities of these O-methyltransferase activities biochemically rationalizes the variation in the composition of the essential oils of these chemotypes.

Journal Article↗
PubMed1997

Antianaphylactic properties of eugenol.

The effects of eugenol, a major component of clove, on anaphylaxis were evaluated in rats. Eugenol inhibited compound 48/80-induced systemic anaphylaxis 100% with a dose of 10 micrograms g-1 body weight (BW). While serum levels of histamine were markedly elevated after compound 48/80 injection in all groups of rats, rats injected with eugenol showed a significant reduction in serum histamine levels. Eugenol also inhibited passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE. Eugenol dose-dependently inhibited histamine release from the rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The morphological examination clearly showed that eugenol prevented the anaphylactic degranulation of RPMC. Moreover, Eugenol (10 micrograms ml-1) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha production. These results suggest that eugenol has antianaphylactic properties by preventing mast cell degranulation.

Anaphylaxis↗
PubMed1988

Acute inhalation toxicity of eugenol in rats.

The acute toxicity of inhaled eugenol was assessed by exposure of three groups of five male and five female rats to a submicron aerosol of eugenol for 4 h followed by a 14-day observation period. A fourth group, also of five male and five female rats and exposed to air only under similar conditions, served as a control group for comparison. The three concentrations of eugenol to which the different groups were exposed were 2.58, 1.37 and 0.77 mg/l. The mass median aerodynamic diameters and geometric standard deviations of the aerosols were, respectively, 0.82 micron (sigma g 2.26), 0.88 micron (sigma g 2.05) and 0.9 micron (sigma g 1.87). Clinical signs observed during exposure consisted principally of moderately increased salivation and restlessness (indicative of irritation) and abnormal breathing patterns. The signs were graded, being less marked in animals exposed to the lower concentrations of eugenol. All three groups, exposed to high, medium and low levels of eugenol, lost weight overnight following exposure. Associated with the weight loss were marked reductions in food and water intake. The responses appeared to be largely independent of the concentration of eugenol inhaled, although there was some evidence of a graded effect on water intake. There was rapid recovery, with food and water consumption data comparable with control values throughout most of the remainder of the 14-day observation period. Also, by the end of the observation period, group mean body weights were comparable. Upon sacrifice and macroscopic examination of the animals, abnormalities were detected in the lungs only of a few animals: 3/10 control, 2/10 eugenol 2.58 mg/l, and 2/10 eugenol 0.77 mg/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed2006

Potential of Rhodococcus strains for biotechnological vanillin production from ferulic acid and eugenol.

The potential of two Rhodococcus strains for biotechnological vanillin production from ferulic acid and eugenol was investigated. Genome sequence data of Rhodococcus sp. I24 suggested a coenzyme A-dependent, non-beta-oxidative pathway for ferulic acid bioconversion, which involves feruloyl-CoA synthetase (Fcs), enoyl-CoA hydratase/aldolase (Ech), and vanillin dehydrogenase (Vdh). This pathway was proven for Rhodococcus opacus PD630 by physiological characterization of knockout mutants. However, expression and functional characterization of corresponding structural genes from I24 suggested that degradation of ferulic acid in this strain proceeds via a beta-oxidative pathway. The vanillin precursor eugenol facilitated growth of I24 but not of PD630. Coniferyl aldehyde was an intermediate of eugenol degradation by I24. Since the genome sequence of I24 is devoid of eugenol hydroxylase homologous genes (ehyAB), eugenol bioconversion is most probably initiated by a new step in this bacterium. To establish eugenol bioconversion in PD630, the vanillyl alcohol oxidase gene (vaoA) from Penicillium simplicissimum CBS 170.90 was expressed in PD630 together with coniferyl alcohol dehydrogenase (calA) and coniferyl aldehyde dehydrogenase (calB) genes from Pseudomonas sp. HR199. The recombinant strain converted eugenol to ferulic acid. The obtained data suggest that genetically engineered strains of I24 and PD630 are suitable candidates for vanillin production from eugenol.

Bacterial Proteins↗
PubMed1984

Effects of eugenol on rat phrenic nerve and phrenic nerve-diaphragm preparations.

The compound-action potential (cAP) of the nerve evoked at 1 Hz was reversibly inhibited and the threshold for nerve stimulation increased between 0.065 and 0.97 mM eugenol. The inhibition showed a sigmoid log10 dose-response relationship. With 2.44 mM or higher concentrations the block became irreversible. The inhibition was enhanced during stimulation at 100 Hz in 5 s with 0.487 mM or higher concentrations. The muscle tetanic tension also showed this high frequency inhibition (HFI). After 40-min exposure to 0.65 mM eugenol, the twitch contractions were unaffected. The indirectly induced tetanic tension was inhibited to 16.6 per cent of control in the initial and to 0.5 per cent in the terminal phase of a 5-s period of 100-Hz stimulation, whereas the directly-induced tetanic tension was inhibited to 38.0 and 13.6 per cent, respectively. Thus, eugenol had affected the neuromuscular transmission during tetanic stimulation in addition to its effect on the directly-stimulated preparation. Intracellular recordings of the end-plate potential (EPP) and miniature end-plate potential (MEPP) indicated both a pre- and a post-synaptic mechanism of action for eugenol. Experiments with eugenol plus d-tubocurarine showed a synergistic effect between these two drugs, suggesting a curare-like effect by eugenol. The resting membrane potential of the muscle was unaffected by eugenol. The following findings suggest that eugenol is a membrane-stabilizing (local anaesthetic) drug at low concentrations: reversible cAP inhibition, increased threshold, high-frequency inhibition, and unresponsiveness of the resting membrane potential of the muscle to the drug.

Action Potentials↗
PubMed1988

Enhancement of UDP-glucuronyltransferase, UDP-glucose dehydrogenase, and glutathione S-transferase activities in rat liver by dietary administration of eugenol.

Male Fisher rats were fed a diet ad lib. containing eugenol (4-allyl-2-methoxyphenol) to observe its effects on liver drug-detoxifying enzymes such as UDP-glucuronyltransferase (GT), UDP-glucose dehydrogenase (DH) and glutathione S-transferase (GST). Liver weights were not affected significantly by a diet containing 3% eugenol (w/w) for 13 weeks. The activities of GT of liver microsomes toward various xenobiotic substances such as 4-nitrophenol, 1-naphthol, 4-hydroxybiphenyl and 4-methylumbelliferone were enhanced by dietary administration of eugenol, but the activity of GT toward its endogenous substrate, bilirubin, was not changed. Dose-response relationships between the enhancement of GT activities toward these xenobiotics and the dose of eugenol were observed. The induced higher activities of GT toward these xenobiotics were maintained during 13 weeks of eugenol treatment. Similar results on DH and GST activities in the liver cytosol were obtained by dietary administration of eugenol, while no effect on cytochrome P-450 content in the liver microsomes from the rats fed the eugenol diet was observed during 13 weeks. These results suggest that the intracellular content of the active intermediates of various drugs or carcinogens would be reduced by this specific enhancement of drug-detoxifying enzymes in the liver of rats given a diet containing eugenol, as previously described for a diet containing 2(3)-tert-butyl-4-hydroxyanisole (BHA) [Y-N. Cha and H. S. Heine, Cancer Res. 42, 2609 (1982)].

Animals↗
PubMed1983

Eugenol and clove leaf oil: a survey of consumer patch-test sensitization.

The potential of eugenol and of clove leaf oil, which contains a high concentration of eugenol, to induce delayed skin hypersensitivity or to elicit reactions due to pre-existing skin sensitization in man was evaluated by analysing patch-test data. Results from a total of 11,632 patch tests on eugenol itself, on various consumer products containing eugenol and/or clove leaf oil, and on fragrance blends containing eugenol and/or clove leaf oil were collected from fragrance and formulation companies. One instance of induced hypersensitivity and one instance of pre-existing sensitization were observed at eugenol patch-test concentrations of 5 X 10(-2) and 9 X 10(-2)% respectively. In both cases, subsequent patch testing showed skin responses to mixtures of eugenol and isoeugenol, but no further attempt was made to define the causative agent. The survey indicates that, at the concentrations present in consumer products, eugenol alone or as part of clove leaf oil has a very low potential either to elicit pre-existing sensitization ('elicited' reactions) or to induce hypersensitivity ('induced' reactions).

Dermatitis, Contact↗
PubMed2003

Vasorelaxant effects of eugenol on rat thoracic aorta.

Eugenol is a natural pungent substance and the main component of clove oil, with vasorelaxant action. To elucidate some of the possible mechanisms involved in this action isometric tension was measured in aortic rings from male Wistar rats precontracted with phenylephrine (PHE, 10(-7) M) or KCl (75 mM). Responses to increasing concentrations of eugenol (10(-6)-10(-2) M) were obtained in the presence and absence of endothelium. In the presence of eugenol, dose-response curves to PHE (10(-9) to 10(-4) M) and KCl (5-125 mM) were displaced downwards. Concentration-dependent relaxation was observed in rings precontracted with PHE (10(-7) M) and KCl (75 mM). The tension increment produced by increasing external calcium concentration (0.25-3 mM) was also reduced by eugenol (300 microM) treatment. The inhibitory effects of eugenol (300 microM) were compared to those induced by nifedipine (0.01 microM), a selective Ca(2+) channel blocker, producing similar relaxant effects. Two other protocols were performed. After precontraction with PHE (10(-7) M), increasing concentrations of eugenol (10(-6)-10(-2) M) were used before and after N(w)-nitro-L-arginine (L-NAME, 10(-4) M) and methylene blue (10(-5) M) treatment. Eugenol-induced relaxation was reduced by endothelial damage (rubbing), L-NAME and methylene blue treatments. Results suggested that eugenol produces smooth muscle relaxation resulting from the blockade of both voltage-sensitive and receptor-operated channels that are modulated by endothelial-generated nitric oxide.

Animals↗
PubMed1986

Evaluation of eugenol for mutagenicity by the mouse micronucleus test.

Mutagenicity of eugenol (2-methoxy-4-allylphenol) was evaluated by an in vivo eukaryotic assay in mice. A 50% lethal dose (LD50) for intraperitoneal (IP) delivery of eugenol was found to be 1109.6 mg/kg body weight (7.5% eugenol-in-saline). Oral (PO) delivery via stainless-steel, esophageal cannulation was not lethal to 14,794 mg/kg body weight (100%) eugenol. Based upon recommended procedure, 80 and 25% LD50 doses were administered IP in 250 microliter volumes. Undiluted eugenol was administered PO in 100 microliter volumes. Delivery of eugenol by both regimes to male mice induced anaphase mutations in polychromatic erythrocytes as measured by the bone marrow micronucleus test. IP delivery of both doses induced the formation of micronuclei to significant levels (P less than 0.001) compared to saline controls. PO delivery of eugenol induced a much reduced frequency of micronuclei when compared to the IP route. However, a significant increase in micronuclei was evident when this test population was compared to its control group (P less than 0.003). These results suggest that eugenol presents some mutagenic capacity in eukaryotic hosts and should be evaluated for further toxicological effects.

Administration, Oral↗
PubMed1997

Eugenol activates Ca(2+)-permeable currents in rat dorsal root ganglion cells.

Although little is known about the mechanism of action of eugenol, some related compounds have been compared with capsaicin derivatives in terms of the relationship between their chemical structure and activity. To elucidate whether eugenol and capsaicin act via a common mechanism at the neuronal membrane, we investigated the effects of eugenol on rat DRG neurons using the whole-cell patch-clamp technique. Eugenol (0.125-1 mmol/L) produced an inward current in a concentration-dependent manner. The reversal potential for this inward current was around 0 mV in PSS. In Na(+)-deficient solutions, the amplitude of the inward current was slightly reduced at negative holding potentials, whereas in Ca(2+)-free solution, it was markedly reduced at all holding potentials tested. The reversal potential was not changed by superfusion with either solution. Niflumic acid (100 mumol/L) produced a significant inhibition of the current without a change in the reversal potential. These results suggest that eugenol activates a Ca(2+)-permeable channel as well as a Cl- channel. The latter channel may have been activated by the increase in intracellular Ca2+ concentration caused by the activation of the Ca(2+)-permeable channel. Capsazepine (10 mumol/L) partially inhibited the eugenol-induced current and completely inhibited the capsaicin-induced current. Eugenol (1 mmol/L) produced an inward current even after occurrence of desensitization of the capsaicin-induced current had occurred. Our results suggest that eugenol activates a Ca(2+)-permeable ion channel in rat DRG neurons through two different mechanisms: a capsaicin receptor-mediated pathway and a pathway independent of the capsaicin-receptor.

Animals↗
PubMed2003

Interaction between 2-ethoxybenzoic acid (EBA) and eugenol, and related changes in cytotoxicity.

The liquid of 2-ethoxybenzoic acid cements is composed of 2-ethoxybenzoic acid and eugenol (4-allyl-2-methoxyphenol). Recently, eugenol was reported to produce radicals at a higher pH, which consequently directly damages cells. We examined here whether eugenol radicals are generated from the mixture of eugenol/calcium hydroxide, and also whether 2-ethoxybenzoic acid or acetylsalicylic acid scavenges radicals, using electron spin resonance spectroscopy. Radicals were generated from the mixture of eugenol/calcium hydroxide in 50% dimethylsulfoxide solution. The radical intensity of eugenol in 50% dimethylsulfoxide with 0.1 M sodium bicarbonate buffer (pH 9.5) was dose-dependently reduced by 2-ethoxybenzoic acid, whereas it was enhanced by acetylsalicylic acid. Next, we investigated the cytotoxic effect of eugenol on 2-ethoxybenzoic acid, acetylsalicylic acid, or calcium hydroxide on human pulp fibroblasts or a human submandibular gland cancer cell line. The cytotoxicity of EBA was decreased, whereas that of acetylsalicylic acid was increased by eugenol. In contrast, that of calcium hydroxide was not affected by eugenol. Human pulp fibroblast but not human submandibular gland cells showed a high resistance against calcium hydroxide. The generation of eugenol radicals in the liquid of 2-ethoxybenzoic acid cements caused by oxidation may be suppressed by 2-ethoxybenzoic acid.

Aspirin↗
PubMed2006

Eugenol inhibits sodium currents in dental afferent neurons.

Although eugenol is widely used in dentistry, little is known about the molecular mechanisms responsible for its anesthetic properties. In addition to calcium channels, recently demonstrated by our group, there could be another molecular target for eugenol. Using a whole-cell patch-clamp technique, we investigated the effect of eugenol on voltage-gated sodium channel currents (I(Na)) in rat dental primary afferent neurons identified by retrograde labeling with a fluorescent dye in maxillary molars. Eugenol inhibited action potentials and I(Na) in both capsaicin-sensitive and capsaicin-insensitive neurons. The pre-treatment with capsazepine, a competitive antagonist of transient receptor potential vanilloid 1 (TRPV1), failed to block the inhibitory effect of eugenol on I(Na), suggesting no involvement of TRPV1. Two types of I(Na), tetrodotoxin (TTX)-resistant and TTX-sensitive I(Na), were inhibited by eugenol. Our results demonstrated that eugenol inhibits I(Na) in a TRPV1-independent manner. We suggest that I(Na) inhibition by eugenol contributes to its analgesic effect.

Action Potentials↗
PubMed2003

Endothelium-dependent and -independent vasodilator effects of eugenol in the rat mesenteric vascular bed.

The possible involvement of the endothelium in the vasodilator action of eugenol was investigated in the mesenteric vascular bed (MVB) of the rat. Bolus injections of eugenol (0.2, 2 and 20 micromol) and acetylcholine (ACh; 10, 30 and 100 pmol) induced dose-dependent vasodilator responses in noradrenaline-precontracted beds that were partially inhibited by pretreatment of the MVB with deoxycholate (1 mg mL(-1)) to remove the endothelium (approximately 14% and approximately 30% of the control response remaining at the lowest doses of ACh and eugenol, respectively). The vasodilator effect of glyceryl trinitrate (1 micromol) was unaltered by deoxycholate. In the presence of either N(omega)-nitro-L-arginine methyl ester (300 microM) or tetraethylammonium (1 mM)the response to ACh was partially reduced, whereas eugenol-induced vasodilation was unaffected. Similarly the vasodilator effect of eugenol was not inhibited by indometacin (3 microM). Under calcium-free conditions the vasoconstrictor response elicited by bolus injections of noradrenaline (10 nmol) was dose-dependently and completely inhibited by eugenol (0.1-1 mM). Additionally, the pressor effects of bolus injections of calcium chloride in potassium-depolarized MVBs were greatly reduced in the presence of eugenol (0.1 mM), with a maximal reduction of approximately 71% of the control response. Our data showed that eugenol induced dose-dependent, reversible vasodilator responses in the rat MVB, that were partially dependent on the endothelium, although apparently independent of nitric oxide, endothelium-derived hyperpolarizing factor or prostacyclin. Furthermore, an endothelium-independent intracellular site of action seemed likely to participate in its smooth muscle relaxant properties.

Acetylcholine↗
PubMed2005

Stability and antimicrobial efficiency of eugenol encapsulated in surfactant micelles as affected by temperature and pH.

Growth inhibition of four strains of Escherichia coli O157:H7 (H1730, F4546, 932, and E0019) and Listeria monocytogenes (Scott A, 101, 108, and 310) by eugenol encapsulated in water soluble micellar nonionic surfactant solutions (Surfynol 485W) adjusted to pH 5, 6, and 7 and incubated at 10, 22, and 32 degrees C was determined. Concentrations of eugenol ranged from 0.2 to 0.9% at a surfactant concentration of 5%. Antimicrobial activity was assessed using a microbroth dilution assay. Eugenol encapsulated in surfactant micelles inhibited both microorganisms at pH 5, 6, and 7. At pH 5, some inhibition occurred in the absence of eugenol, i.e., by the surfactant itself (optical density at 24 h for L. monocytogenes = 0.07 and optical density at 24 h for E. coli O157:H7 = 0.09), but addition of >0.2% eugenol led to complete inhibition of both microorganisms. Inhibition of L. monocytogenes and E. coli O157:H7 decreased with increasing pH, that is, the minimum inhibitory concentration was 0.2, 0.5, and 0.5% of micellar encapsulated eugenol solutions at pH 5, 6, and 7, respectively. The encapsulated essential oil component in surfactant micelles was effective at all three temperatures tested (10, 22, and 32 degrees C), indicating that the activity of encapsulated eugenol was not affected by high or low (refrigeration) temperatures. Overall, strains of E. coli O157:H7 were more sensitive than strains of L. monocytogenes. Improved activity was attributed to increased solubility of eugenol in the aqueous phase due to the presence of surfactants and improved interactions of antimicrobials with microorganisms.

Anti-Bacterial Agents↗
PubMed2000

Radical generation, radical-scavenging activity, and cytotoxicity of eugenol-related compounds.

To clarify the possible link between radicals and cytotoxicity of eugenol-related compounds, dimeric compounds were synthesized from eugenol (4-allyl-2-methoxy-phenol), butylated hydroxyanisole (BHA) (2-t-butyl-4-methoxyphenol) or MMP (2 methoxy-4-methylphenol); bis-EUG (3,3'-dimethoxy-5,5'-di-2-propenyl-1,1'-biphenyl-2,2'-diol), bis-BHA (3,3'-di-t-butyl-5,5'-dimethoxy-1,1'-biphenyl-2,2'-diol), and bis-MMP (3,3'-di-methoxy-5,5'-dimethyl-1,1'-biphenyl-2,2'-diol). The cytotoxic activity of these compounds was determined using a salivary gland tumor cell line (HSG), oral squamous cell carcinoma cell line (HSC-2) and human promyelocytic leukemia cell line (HL-60). A parabolic relationship between the cytotoxicity and log P (the octanol-water partition coefficient) was observed, showing that both BHA and bis-MMP, with a log P of 3-4, were the most cytotoxic. The cytotoxic activity of the 2-methoxy derivatives, eugenol, MMP and bis-MMP, against HSG cells was significantly enhanced by visible-light irradiation, possibly due to their high redox potential. Electron spin resonance (ESR) spectroscopy indicated that eugenol and BHA alone produced radicals under alkaline conditions (pH > 9.5), and eugenol most efficiently scavenges reactive oxygen species (O2-). Antioxidative reactivity of eugenol-related compounds was determined by measuring the inhibiting periods of the AIBN (2,2'-azobisisobutyronitrile)/MMA (methyl methacrylate) polymerization system, and the number of moles of peroxy radical trapped by moles of the relevant phenols (stoichiometric factor, n). It was found that the n values of eugenol and MMP were approximately 1, whereas those of BHA >2, suggesting that eugenol and MMP undergo dimerization through radical-radical couplings through quinone methides, whereas BHA undergoes the competitive interaction with poly-MMA radicals after oxidation by AIBN-peroxy radicals. BHA was an efficient peroxy radical-scavenger, but possibly reacted with polymer radicals of the lipid, thus mediating the cytotoxicity. The n value of bis-BHA was two, whereas those of bis-EUG and bis-MMP were 1.6-1.7, suggesting that the latter were further oxidized. The enthalpies of phenoxyl radical formation were determined using the semi-empirical PM3 quantum-mechanical method and the possible link to redox potential was discussed.

Adenocarcinoma↗
PubMed1995

Intravenous eugenol causes hemorrhagic lung edema in rats: proposed oxidant mechanisms.

Although eugenol, the active phenolic constituent of oil of cloves, has been implicated as a cause of noncardiogenic pulmonary edema, the mechanism of lung injury is unknown. We studied the effects of intravenous infusion of eugenol in rats and found that 4 microliters and 8 microliters of eugenol (6.52 mol/L) caused acute respiratory distress with hemorrhagic pulmonary edema. Histologic features included perivascular, interstitial, and alveolar edema with extravasation of red blood cells and neutrophils into the alveolar space and alveolar capillary trapping of neutrophils. In addition, lungs treated with eugenol had increased bronchoalveolar lavage fluid (BALF) protein content, and lung wet-to-dry weight ratios were increased in animals treated with 8 microliters eugenol. Pretreatment with intravenous superoxide dismutase (SOD) or catalase but not dimethylthiourea (DMTU) decreased BALF protein content after infusion of 4 microliters and 8 microliters of eugenol. SOD and catalase but not DMTU decreased lung wet-to-dry weight ratios in animals infused with 8 microliters of eugenol. We conclude that intravenous infusion of eugenol causes hemorrhagic pulmonary edema with intrapulmonary sequestration of neutrophils and suggest that the injury may be at least partly oxidant mediated.

Animals↗