Demétrius Antonio Machado Araújo

Centro Universitário de João Pessoa, Frederícia, Paraíba, Brazil

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Publications (31)53.72 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to investigate the cytotoxic effect of new 1,4-naphthoquinone- 1,2,3-triazoles, named C2 to C8 triazole derivatives, towards human cancer cell lines. The effect on cell viability was assessed by MTT and propidium iodide assays. The cytotoxic effect of C2 and C3 in K562 and HL-60 cells were analyzed by flow cytometry, DNA fragmentation and reactive oxygen species (ROS) production. Western blot and q-PCR procedures were also performed. C2 and C3 inhibited both K562 and HL-60 cells growth in a concentration-dependent manner. C2 presented the highest cytotoxic activity with an IC50 of approximately 14 μm and 41 μm for HL-60 and K562 cells, respectively, while being less toxic to normal peripheral blood monocyte cells. Both derivatives induced cellular changes in HL-60 cells, characteristic of apoptosis, such as mitochondrial membrane depolarization, phosphatidylserine externalization, increasing sub-G1 phase, DNA fragmentation, downregulating Bcl-2 protein and upregulating Bax protein. In K562 cells, C2 and C3 induced S-phase arrest of cell cycle, which was associated with upregulation of p21. The effect of these derivatives in HL-60 cells can be related to the ROS intracellular level. Taken together our results showed that C2 and C3 triazole derivatives presented the best potential for drug design. © 2015 Royal Pharmaceutical Society.
    No preview · Article · Aug 2015
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    ABSTRACT: Chlorhexidine (CHX) is regarded as one of the most successful antiplaque agents in controlling the formation of dental biofilm. Nevertheless, molecular mechanisms of their effects in Streptococcus mutans are largely unknown. In this work, the effects of sub-lethal and lethal concentrations of chlorhexidine (CHX) on planktonic or biofilm-organized Streptococcus mutans cells were investi-gated in dose-and time-dependent manner. The Minimum Inhibitory Concentration (MIC) and the Minimum Bactericidal Concentration (MBC) for planktonic cells and biofilm conditions were de-termined by standard methods. Quantitative PCR (qPCR) was used to quantify the relative levels of glucosyltransferase B (gtfB), gtfC and gtfD transcription of S. mutans in the presence of CHX. The CHX activity in the initial biofilm structure and morphological alterations in planktonic cells were examined by Scanning Electron Microscopy (SEM). The results indicate that CHX increased ex-pression of gtfC and gtfD in planktonic S. mutans cells and CHX reduced the expression of gtfB, gtfC, and gtfD in biofilms. High concentrations of CHX resulted in several wilted S. mutans planktonic cells with spilled intracellular material, while decreased cells' chain length and matrix was found when the initial biofilm was exposed to increasing concentrations of CHX. CHX's effects against * Corresponding author. A. C. B. da Silva et al. 946 bacteria depend on the type of growth organization and the concentration and time of exposure to the drug. At sub-lethal concentrations, CHX affects the expression of glucosyltransferases, which may have anticariogenic effect.
    No preview · Article · Oct 2014 · Advances in Microbiology
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    ABSTRACT: Natural products are still been explored to provide new molecules that could interact with known and unknown pharmacological targets. Medicinal chemists have put a lot of effort in order to validate highly selective and potent biological agents. The studies focusing on the understanding of how these molecules act are very important and relevant to the field. A number of studies have shown that menthol possesses a large spectrum of biological activities. Interestingly, menthol has been implicated in the generation of an inward cationic current related to temperature sensing and this fact has been the focus of attention of various research groups around the world. In this chapter, we will provide information of menthol’s pharmacological profile in different tissues. We also discuss the cytotoxic effects that have been attributed to menthol and many groups have provided evidence to confirm that this cytotoxicity is somehow related to the activation of TRPM8 ion channels and it seems to be dependent on intracellular calcium handling.
    No preview · Chapter · Jan 2013
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    Full-text · Dataset · Nov 2012
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    ABSTRACT: Curine is a novel bisbenzylisoquinoline alkaloid that has previously been reported as a vasodilator. The underlying mechanism(s) of the vasodilator effect of curine remains to be characterized. In this study, we investigated the cellular mechanism that is responsible for the vasodilator effect of curine in the rat aorta. The vasorelaxant activity of curine was recorded using a myograph. Ca2+ currents in A7r5 cells were measured using the whole-cell patch-clamp technique. Intracellular Ca2+ transients were determined using confocal microscopy. In a concentration-dependent manner, curine inhibited contractions elicited by high extracellular K+ and Bay K8644 in the rat aorta and reduced the rise in the intracellular Ca2+ concentration induced by membrane depolarization in response to an increase in extracellular K+ concentration in vascular smooth muscle cells. Moreover, curine decreased the peak amplitude of L-type Ca2+ currents (ICa,L) in a concentration-dependent manner without changing the characteristics of the current density vs. voltage relationship and the steady-state activation of ICa,L. Furthermore, curine shifted the steady-state inactivation curve of ICa,L toward more hyperpolarized membrane potentials. None of the following modified the effect of curine on ICa,L amplitude: 3-isobutyl-1-methylxanthine, an inhibitor of phosphodiesterases; dibutyryl cyclic AMP, an activator of protein kinase A (PKA); or 8-Br-cyclic GMP, an activator of protein kinase G (PKG). Our results showed that curine inhibited the L-type voltage-dependent Ca2+ current in rat aorta smooth muscle cells, which caused a decrease in intracellular global Ca2+ transients that led to vasorelaxation.
    Full-text · Article · Nov 2011 · European journal of pharmacology
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    ABSTRACT: Canavalia ensiformis (ConA), Canavalia brasiliensis (Conbr), and Cratylia floribunda (CFL) lectins have exhibited glucose-mannose binding specificity. We investigated the effect of fetal bovine serum (FBS) concentrations (1, 5, 10, and 20%) on the cytotoxic effect of these lectins against breast tumor cell line MCF-7. Cell viability was examined using the MTT reduction assay. When cells were grown in a medium supplemented with a higher serum concentration (10 or 20%), all lectins were much less toxic. When we used 1% FBS, it was possible to achieve a concentration-dependent activity by all examined lectins, with an IC50 of 3.5, 25, and 60 µg/mL for ConA, Conbr, and CFL, respectively. All lectins incubated with 1% FBS induced apoptosis and DNA damage in MCF-7 cells. We conclude that ConA, Conbr, and CFL lectins' cytotoxic and genotoxic effects were observed only at low concentrations of serum. © 2011 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:290–296, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20388
    No preview · Article · Sep 2011 · Journal of Biochemical and Molecular Toxicology
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    ABSTRACT: Rotundifolone is the major constituent of the essential oil of Mentha x villosa Hudson. In preliminary studies, rotundifolone induced significant hypotensive, bradycardic and vasorelaxant effects in rats. Thus, to gain more insight into the pharmacology of rotundifolone, the aim of this study was to characterize the molecular mechanism of action involved in relaxation produced by rotundifolone. The relaxant effect was investigated in rat superior mesenteric arteries by using isometric tension measurements and whole-cell patch-clamp techniques. Rotundifolone relaxed phenylephrine-induced contractions in a concentration-dependent manner. Pre-treatment with KCl (20 mM), charybdotoxin (10(-7) M) or tetraethylammonium (TEA 10(-3) or 3 × 10(-3) M) significantly attenuated the relaxation effect induced by rotundifolone. Additionally, whole-cell patch-clamp recordings were made in mesenteric smooth muscle cells and showed that rotundifolone significantly increased K(+) currents, and this effect was abolished by TEA (10(-3)  M), suggesting the participation of BK(Ca) channels. Furthermore, rotundifolone inhibited the vasoconstriction induced by CaCl(2) in depolarizing nominally Ca(2+) -free medium and antagonized the contractions elicited by an L-type Ca(2+) channel agonist, S(-)-Bay K 8644 (2 × 10(-7)  M), indicating that the vasodilatation involved inhibition of Ca(2+) influx through L-type voltage-dependent calcium channels (Ca(v) type-L). Additionally, rotundifolone inhibited L-type Ca(2+) currents (I(Ca) L), affecting the voltage-dependent activation of I(Ca) L and steady-state inactivation. Our findings suggest that rotundifolone induces vasodilatation through two distinct but complementary mechanisms that clearly depend on the concentration range used. Rotundifolone elicits an increase in the current density of BK(Ca) channels and causes a shift in the steady-state inactivation relationship for Ca(v) type-L towards more hyperpolarized membrane potentials.
    Full-text · Article · Jul 2011 · Basic & Clinical Pharmacology & Toxicology
  • Demetrius Antonio Machado de Araújo · Christiane Freitas · Jader Santos Cruz
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    ABSTRACT: The discovery and development of new drugs targeting voltage-gated ion channels are important for treating a variety of medical conditions and diseases. Ion channels are molecular nanostructures expressed ubiquitously throughout the whole body, and are involved in many basic physiological processes. Over the years, natural products have proven useful in the pharmacological assessment of ion channel structure and function, while also contributing to the identification of lead molecules for drug development. Essential oils are complex chemical mixtures isolated from plants which may possess a large spectrum of biological activities most of them of clinical interest. Among their bioactive constituents, terpenes are small to medium-sized components and belong to different chemical groups. Various reports have drawn our attention to the fact that terpenes are novel compounds targeting voltage-gated ion channels. The purpose of this review is to provide a focused discussion on the molecular interaction between monoterpenes and phenylpropenes with voltage-gated ion channels in different biological scenarios.
    No preview · Article · May 2011 · Life sciences
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    ABSTRACT: Carvone (p-mentha-6,8-dien-2-one) is a monoterpene ketone found as the main active component of various essential oils. It is obtained by distillation and occurs naturally as the enantiomers (+)- and (-)-carvone. Our group have shown that the in vivo antinociceptive activity of (-)-carvone is impaired with decreased nerve excitability. To better characterize the neuropharmacology of such a monoterpene, we investigated the profile of several carvone analogues to establish a structure-function relationship related to the compound action potential (CAP) inhibitory effect. We performed ex vivo assays to evaluate the effects of (+)- and (-)-carvone, carvacrol, (-)-carveol, and limonene on CAP characteristics using a modified single sucrose-gap method. Our results demonstrated that (-)-carvone was less potent (IC(50)=10.7+/-0.07 mM) in reducing nerve excitability than its enantiomer, (+)-carvone (IC(50)=8.7+/-0.1mM), although they shared a similar mode of action, since their effects were partially extinguished by nerve washing and also by reduction of depolarization velocity, probably as a result of voltage-gated sodium channel blockades. In a structure-activity relationship study, we demonstrated that hydroxyl groups in the (-)-carveol and carvacrol molecules enhanced the CAP blocking-effect, while the absence of oxygen moiety in (+)-limonene resulted in the effect being almost abolished. Therefore, inhibition of CAP conduction in peripheral nerves by monoterpenes could expand our understanding concerning the pharmacology of such natural bioactive compounds. Moreover, activation or inhibition of nerve excitability with these tested monoterpenes can be achieved by altering their chemical structures, and this can lead to further implications for target-directed drug design.
    No preview · Article · Oct 2010 · European journal of pharmacology
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    ABSTRACT: We investigated the antinociceptive and nerve excitability effects of the N-salicyloyltryptamine (NST) NST-treated mice exhibited a significant decrease in the number of writhes when 100 and 200 mg/kg (i.p.) were administered (i.p.). This effect was not antagonized by naloxone (1.5 mg/kg, i.p.). NST inhibited the licking response of the injected paw when 100 and 200 mg/kg were administered (i.p.) to mice in the first and second phases of the formalin test. Because the antinociceptive effects could be associated with neuronal excitability inhibition, we performed the single sucrose gap technique and showed that NST (3.57 mM) significantly reduced (29.2%) amplitude of the compound action potential (CAP) suggesting a sodium channel effect induced by NST. Our results demonstrated an antinociceptive activity of the NST that could be, at least in part, associated to the reduction of the action potential amplitude. NST might represent an important tool for pain management.
    Full-text · Article · Oct 2010 · BioMed Research International
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    ABSTRACT: To evaluate the antinociceptive effects of citronellal (CTL) on formalin-, capsaicin-, and glutamate-induced orofacial nociception in mice and to investigate whether such effects might involve a change in neural excitability. Male mice were pretreated with CTL (50, 100, and 200 mg/kg, ip), morphine (5 mg/kg, ip), or vehicle (distilled water plus one drop of Tween 80 0.2%) before formalin (20 microL, 2%), capsaicin (20 microL, 2.5 microg) or glutamate (40 microL, 25 microM) injection into the right vibrissa. Sciatic nerve recordings were made using the single sucrose gap technique in rats. The data obtained were analyzed by ANOVA followed by Dunnett's test for the behavioral analyses and by the Student t test for CAP evaluation. Pretreatment with CTL was effective in reducing nociceptive face-rubbing behavior in both phases of the formalin test, which was also naloxone-sensitive. CTL produced significantly antinociceptive effect at all doses in the capsaicin- and glutamate- tests. Rota-rod testing indicated that such results were unlikely to be provoked by motor abnormality. Recordings using the single sucrose gap technique revealed that CTL (10 mM) could reduce the excitability of the isolated sciatic nerve through a diminution of the compound action potential amplitude by about 42.4% from control recordings. These results suggest that CTL might represent an important tool for management and/or treatment of orofacial pain.
    Full-text · Article · Jun 2010 · Journal of orofacial pain
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    ABSTRACT: Essential oils are natural, complex and multi-component systems composed mainly of terpenes in addition to some other non-terpenes compounds that are widely used to prevent and treat human diseases. (-)-alpha-Bisabolol is an unsaturated monocyclic sesquiterpene alcohol found as the major constituent of many essential oils, like the German chamomile (Chamomilla recutita (L.) Rauschert), a plant reported to reduce the perception of acute pain and used for centuries for their medicinal properties. Recently, our group demonstrated the antinociceptive-like effect promoted by other terpenes could be associated with the decreased peripheral nerve excitability. Therefore, this study investigated the pharmacological activities of (-)-alpha-bisabolol on mice peripheral nervous system observing the changes on the compound action potential (CAP) characteristics. Using modified single sucrose-gap method in mice sciatic nerves, we acquired CAP recordings in the absence and presence of (-)-alpha-bisabolol (0.5, 1, 5 and 10mM). We observed that this sesquiterpene was able to reduce the neuronal excitability in a concentration-dependent manner, although, such effects were not reversed when the nerve was submitted to wash out. Assessing CAP parameters of depolarization and repolarization, we noticed similarities between (-)-alpha-bisabolol and lidocaine but not with 4-aminopyridine that are considered good blockers for sodium and potassium voltage-gated channels, respectively. Additionally, we also characterized the non-use-dependent profile of (-)-alpha-bisabolol action, in contrast to lidocaine. Thus, we suggested that decreased nervous excitability elicited by (-)-alpha-bisabolol might be caused by an irreversible blockade of voltage-dependent sodium channels.
    No preview · Article · Mar 2010 · Neuroscience Letters
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    ABSTRACT: The aim of the present study was to determine the natural fluoride levels in the drinking water supplies of a tropical area of Brazil to identify the cities at risk of high prevalence of dental fluorosis and to provide data for future water fluoridation projects in the region. The present study was carried out in Paraíba, in the north-eastern region of Brazil. A total of 223 cities were selected, and local health workers were instructed to collect three samples of drinking water: one from the main public water supply and the other two from a public or residential tap with the same water source. Fluoride analyses were carried out in duplicate using a fluoride-specific electrode coupled to an ion analyser. A total of 167 cities (75%) provided water samples for analysis. Fluoride levels ranged from 0.1 to 1.0 ppm (mg/l). Samples from most of the cities (n = 163, 73%) presented low levels of fluoride (< 0.5 mg/l). Samples from three cities (a total estimate of 28,222 inhabitants exposed) presented 'optimum' fluoride levels (0.6 to 0.8 mg/l). Samples from one city (16,724 inhabitants) with 1.0 mg/l of fluoride in the water were above the recommended level (0.7 mg/l) for the local temperature. It can be concluded that the cities in this area of Brazil presented low natural fluoride levels in the drinking water and could implement controlled water fluoridation projects when technical requirements are accomplished. A high or a moderate prevalence of dental fluorosis due to the intake of natural fluoride in the drinking water is likely to take place in one city only.
    No preview · Article · Jan 2010 · Oral health & preventive dentistry
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    ABSTRACT: AIM: In the present study we verified the anticonvulsant properties of the new tryptamine analogue, N-salicyloyltryptamine (NST), in rodents. METHODS AND RESULTS: In the evaluation of the anticonvulsant activity, NST protected the animals from the incidence of seizures induced by pentylenetetrazole (PTZ) and picrotoxin (PIC), in doses of 100 and 200 mg/kg. NST (100 and 200 mg/kg, i.p.) significantly eliminated the extensor reflex of maximal electric-induced seizure tests in 40% of the experimental animals. However, in the PTZ model FLU (10 mg/kg, i.p.), an antagonist of the benzodiazepine (BZD) site in the GABAA-BZD receptor complex, inhibited the prolongation of seizure latency induced by NST. CONCLUSION: Our results demonstrated an anticonvulsant activity of the new analogue that could be, at least in part, associated to the involvement of the GABAergic mechanism.
    Full-text · Article · Dec 2009 · Journal of Epilepsy and Clinical Neurophysiology
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    ABSTRACT: Aniba rosaeodora is an aromatic plant which has been used in Brazil folk medicine due to its sedative effect. Therefore, the purpose of the present study was to evaluate the sedative effect of linalool-rich rosewood oil in mice. In addition we sought to investigate the linalool-rich oil effects on the isolated nerve using the single sucrose-gap technique. Sedative effect was determined by measuring the potentiation of the pentobarbital-induced sleeping time. The compound action potential amplitude was evaluated as a way to detect changes in excitability of the isolated nerve. The results showed that administration of rosewood oil at the doses of 200 and 300 mg/kg significantly decreased latency and increased the duration of sleeping time. On the other hand, the dose of 100 mg/kg potentiated significantly the pentobarbital action decreasing pentobarbital latency time and increasing pentobarbital sleeping time. In addition, the effect of linalool-rich rosewood oil on the isolated nerve of the rat was also investigated through the single sucrose-gap technique. The amplitude of the action potential decreased almost 100% when it was incubated for 30 min at 100 microg/ml. From this study, it is suggested a sedative effect of linalool-rich rosewood oil that could, at least in part, be explained by the reduction in action potential amplitude that provokes a decrease in neuronal excitability.
    Full-text · Article · Jul 2009 · Journal of ethnopharmacology
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    Andréa Cristina Barbosa da Silva · Jader Dos Santos Cruz · Fábio Correia Sampaio · Demetrius Antônio Machado de Araújo
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    ABSTRACT: This work correlated the presence of oral streptococci in dental biofilm with clinical indexes of caries and oral hygiene in caries-active and caries-free children. S. mutans and/or S. sobrinus in the dental biofilm does not indicate a direct risk for developing dental caries.
    Full-text · Article · Oct 2008 · Brazilian Journal of Microbiology
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    ABSTRACT: In Brazil, various species of the genus Ocotea are used in folk medicine for treating several diseases. The chemical characterization of this plant showed the presence of alkaloids belonging to the benzyltetrahydroisoquinoline family, the major component of which is (S)-reticuline. The present study investigated whether (S)-reticuline exerts an inhibitory effect on smooth muscle L-type Ca2+ channels. Tension measurements and patch clamp techniques were utilized to study the effects of (S)-reticuline. Whole-cell Ca2+ currents were measured using the A7r5 smooth muscle cell line. (S)-reticuline antagonized CaCl2- and KCl-induced contractions and elicited vasorelaxation. It also reduced the voltage-activated peak amplitude of I Ca,L in a concentration-dependent manner. (S)-reticuline did not change the characteristics of current density vs. voltage relationship. (S)-reticuline shifted leftwards the steady-state inactivation curve of I Ca,L. The application of dibutyryl cyclic adenosine monophosphate to the cell decreased the amplitude of Ca2+ currents. In cells pretreated with forskolin, an adenylate cyclase activator, the addition of (S)-reticuline caused further inhibition of the Ca2+ currents suggesting an additive effect. The results obtained show that (S)-reticuline elicits vasorelaxation probably due to the blockade of the L-type voltage-dependent Ca2+ current in rat aorta. The reported effect may contribute to the potential cardioprotective efficacy of (S)-reticuline.
    Full-text · Article · Oct 2008 · Archiv für Experimentelle Pathologie und Pharmakologie
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    ABSTRACT: The anticonvulsant effect of alpha,beta-epoxy-carvone (EC), a monoterpene monocyclic, was investigated in three animal models. EC at 300 or 400 mg/kg promoted protection of 75% and 87.5%, respectively, against convulsions induced chemically by pentylenetetrazole (PTZ) and it was efficient in prevents the tonic convulsions induced by maximal electroshock (MES) in doses of 200, 300 or 400 mg/kg, resulting in 25%, 25% and 100% of protection, respectively. This monoterpene was also capable to promote an increase of latency for development of convulsions induced by picrotoxin (PIC) at 300 or 400 mg/kg and presented a significant protection against convulsions at doses of 200, 300 or 400 mg/kg, resulting in 12.5%, 12.5% and 100% of protection, respectively. On the other hand, the anticonvulsant effect of EC, was not affected by pretreatment with flumazenil (FLU), a selective antagonist of benzodiazepine site of GABA(A) receptor. Additionally was observed that EC treatment reduced the levels of in vitro lipoperoxidation and decreased (21.2%) the amplitude of compound action potential after 30 min of incubation. The present results clearly indicate the ability of EC to modulate the anticonvulsant and antioxidant effects. However, our data suggests that the action mechanisms are not due a direct activation of the GABA(A) benzodiazepine receptors, but could be associated with the reduction of isolated nerve excitability, possibly involving a voltage-gated Na(+) channels blockade.
    No preview · Article · Sep 2008 · Neuroscience Letters
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    ABSTRACT: Bothrops erythromelas venom (BeV) has been responsible for many snake accidents in Brazil. We investigated the plasmatic pharmacokinetic of BeV labeled with (131)I in the absence and the presence of anti-Bothrops serum (BAS). A higher percentage of BeV plasmatic radioactivity and longer elimination were found in the presence of BAS. Our results showed a redistribution of venom from the tissue to vascular compartment associated with the treatment of envenomed mice with anti-venom 15 min after venom injection.
    Full-text · Article · Jul 2008 · Toxicon
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    ABSTRACT: (-)-Carvone is a monoterpene ketone that is the main active component of Mentha plant species like Mentha spicata. This study aimed to investigate the antinociceptive activity of (-)-carvone using different experimental models of pain and to investigate whether such effects might be involved in the nervous excitability elicited by others monoterpenes. In the acetic acid-induced writhing test, we observed that (-)-carvone-treated mice exhibited a significant decrease in the number of writhes when 100 and 200 mg/kg was administered. It was also demonstrated that (-)-carvone inhibited the licking response of the injected paw when 100 and 200 mg/kg was administered (i.p.) to mice in the first and second phases of the formalin test. Since naloxone (5 mg/kg, s.c.), an opioid antagonist, showed no influence on the antinociceptive action of (-)-carvone (100 mg/kg), this suggested nonparticipation of the opioid system in the modulation of pain induced by (-)-carvone. Such results were unlikely to be provoked by motor abnormality, since (-)-carvone-treated mice did not exhibit any performance alteration on the Rota-rod apparatus. Because the antinociceptive effects could be associated with neuronal excitability inhibition, we performed the single sucrose gap technique and observed that (-)-carvone (10 mM) was able to reduce the excitability of the isolated sciatic nerve through a diminution of the compound action potential amplitude by about 50% from control recordings. We conclude that (-)-carvone has antinociceptive activity associated with decreased peripheral nerve excitability.
    No preview · Article · Jun 2008 · Biological & Pharmaceutical Bulletin

Publication Stats

483 Citations
53.72 Total Impact Points

Institutions

  • 2014
    • Centro Universitário de João Pessoa
      Frederícia, Paraíba, Brazil
  • 2004-2011
    • Universidade Federal da Paraíba
      • • Laboratório de Tecnologia Farmacêutica
      • • Departamento de Biologia Molecular
      Frederícia, Paraíba, Brazil
  • 2010
    • CEP America
      Emeryville, California, United States
    • Universidade Federal de Sergipe
      • Departamento de Fisiologia
      Aracaju, Sergipe, Brazil
  • 1992
    • Instituto De Ciências Farmacêuticas
      Апаресида ди Гояния, Goiás, Brazil