Pharmacological Potential of cis-jasmone in Adult Zebrafish (Danio rerio).

This study evaluates the pharmacological potential of cis-jasmone (CJ) in adult zebrafish (Danio rerio; aZF). Initially, aZF (n = 6/group) were pretreated (20 µL; p. o.) with CJ (0.1 or 0.3 or 1.0 mg/mL) or vehicle (0.5% Tween 80). The animals were submitted to acute toxicity and locomotion tests, pentylenetetrazole-induced seizure, carrageenan-induced abdominal edema, and cinnamaldehyde-, capsaicin-, menthol-, glutamate-, and acid saline-induced orofacial nociception. The possible mechanisms of anticonvulsant, anxiolytic, and antinociceptive action were evaluated. The involvement of central afferent fibers sensitive to cinnamaldehyde and capsaicin and the effect of CJ on the relative gene expression of TRPA1 and TRPV1 in the brain of aZF were also analyzed, in addition to the study of molecular docking between CJ and TRPA1, TRPV1 channels, and GABAA receptors. CJ did not alter the locomotor behavior and showed pharmacological potential in all tested models with no toxicity. The anticonvulsant effect of CJ was prevented by flumazenil (GABAergic antagonist). The anxiolytic-like effect of CJ was prevented by flumazenil and serotonergic antagonists. The antinociceptive effect was prevented by TRPA1 and TRPV1 antagonists. Chemical ablation with capsaicin and cinnamaldehyde prevented the orofacial antinociceptive effect of CJ. Molecular docking studies indicate that CJ interacted with TRPA1, TRPV1, and GABAA receptors. CJ inhibited the relative gene expression of TRPA1 and TRPV1. CJ has pharmacological potential for the treatment of seizures, anxiety, inflammation, and acute orofacial nociception. These effects are obtained by modulating the GABAergic and serotonergic systems, as well as the TRPs and ASIC channels.

Impact of sex and environmental conditions on the responses to pain in zebrafish / Impacto do sexo e das condições ambientais nas respostas do peixe-zebra à dor

ABSTRACT BACKGROUND AND OBJECTIVES: Adult zebrafish (Danio rerio) has been proposed as a low-cost and simple alternative to the use of rodents in laboratory research on novel compounds with antinociceptive potential. This study aimed to assess whether there is an influence of animal sex and the test environment on the orofacial nociceptive behavior of the adult zebrafish. METHODS: First, cinnamaldehyde, menthol, capsaicin, acidic saline, or glutamate was applied into the lips of the adult male or female zebrafish. Naive groups were included as control. The orofacial nociception was quantified in terms of locomotor activity. In other series of experiments, it was evaluated whether the apparatus, acclimatization, period of test, temperature of the water and color of the open field would alter the nociceptive response to cinnamaldehyde. RESULTS: The nociceptive behavior did not depend on the sex of the animal, apparatus, time the test was performed or the color of the open field. However, acclimatization promoted nociceptive behavior in naive animals and did not alter the nociceptive response to cinnamaldehyde (p<0.01 vs acclimatized naive). The nociception behavior was presented only when the test was performed at a temperature of 26ºC (p<0.01 vs naive). CONCLUSION: The results suggest the need to control the environment and water temperature as an environmental source of variation during the nociceptive behavior test of the adult zebrafish.

RESUMO JUSTIFICATIVA E OBJETIVOS: O peixe-zebra adulto (Danio rerio) tem sido proposto como uma alternativa simples e de baixo custo ao uso de roedores em pesquisas laboratoriais de novos compostos com potencial antinociceptivo. Este estudo teve como objetivo avaliar se há influência do sexo do animal e do ambiente de teste no comportamento nociceptivo orofacial do peixe-zebra adulto. MÉTODOS: Inicialmente, cinamaldeído, mentol, capsaicina, solução salina ácida ou glutamato foi aplicada nos lábios do peixe-zebra adulto masculino ou feminino. Grupos naive foram incluídos como controle. A nocicepção orofacial foi quantificada em termos de atividade locomotora. Em outra série de experimentos, foi avaliado se o aparato, aclimatação, período de teste, temperatura da água e cor do campo aberto alterariam a resposta nociceptiva ao cinamaldeído. RESULTADOS: O comportamento nociceptivo não dependeu do sexo do animal, do equipamento de teste, do horário em que o teste foi realizado ou da cor do campo aberto. No entanto, a aclimatação promoveu comportamento nociceptivo em animais naive e não alterou promoveu comportamento nociceptivo em animais naive e não alterou a resposta nociceptiva ao cinamaldeído (p<0,01 vs naive aclimatado). O comportamento nociceptivo foi verificado apenas quando o teste foi executado a uma temperatura de 26ºC (p<0,01 vs naive). CONCLUSÃO: Os resultados sugerem a necessidade de controlar o ambiente e a temperatura da água como fonte de variação ambiental durante o teste de comportamento nociceptivo do peixe-zebra adulto.

Is the orofacial antinociceptive effect of lectins intrinsically related to their specificity to monosaccharides?

Lectins are proteins of non-immunological origin that may play several biological applications, of which we can highlight the anti-inflammatory and antinociceptive activities. In this work, we evaluated the possible effect of orofacial antinociceptive activity of three plant lectins, Dioclea violacea (DVL - Man/Glc-binding), Vatairea macrocarpa (VML - Gal-binding) and PPL (Parkia platycephala - Man/Glc-binding) in adult zebrafish. Acute nociception was induced by menthol (1.2 µM), or capsaicin (4.93 µM) applied into in the upper lip (5.0 µL) of adult wild zebrafish. Zebrafish were pretreated by intraperitoneal injection (20 µL) with vehicle (Control) or lectins (0.025; 0.05 or 0.1 mg/mL) 30 min before induction. The effect of lectins on zebrafish locomotor behavior was evaluated with the open field test. Naive groups (n = 8) were included in all tests. Our results indicate that only PPL presented antinociceptive induced by capsaicin, suggesting the potential clinical application of PPL as inhibitor of orofacial nociception and that this effect may be due to the modulation of TRPV1 channel. In conclusion, lectins that exhibit affinity to the same or different carbohydrates do not necessarily have an antinociceptive effect on the orofacial nociception model, indicating that the glycan carbohydrate binding pattern may be related to the effect on nociception inhibition.

[Comparative study between the level of discomfort and the acoustic reflex in workers]. / Estudo comparativo entre nível de desconforto e reflexo acústico em trabalhadores.

BACKGROUND: Comparative study between the level of discomfort and the acoustic reflex in workers. AIM: To observe the hearing behavior, through the assessment of the contraction activity of the stapedius muscle and the level of discomfort, of individuals who are and are not exposed to occupational noise, with the aim of identifying the influence of noise in the behavior of the contraction of the stapedius muscle and in the sensibility of hearing. METHOD: This study was developed at the Serviço Social da Indústria - SESI - Ce. A hundred and three adults with normal hearing, male and female, with ages varying from 18 to 45 years were divided in three groups: G1 with 41 adults exposed to noise and who used AIPE; G2 with 32 adults exposed to noise and who did not use AIPE; G3 with 30 adults who were not exposed to noise. Participants were submitted to audiologic evaluation, including the analysis of the acoustic reflex level (ARL) and discomfort level (DL) at the frequencies of 500 HZ, 1000Hz, 2000Hz, 3000Hz, 4000Hz and WN. For the statistical analysis the tests of Mann Whitney, Wilcoxon and Kruskal, with significance levels of 5%, were used. RESULTS: No statistically significant difference was identified for the ARL between the three groups, with mean values ranging from 93 to 103dBHL; the ARL was significantly smaller than the DL, with the mean values of DL varying from 111 to 119 dBHL for G1, from 113 to 120dBHL for G2 and from 106 to 114dBHL for G3; the DL is higher in individuals of G1 followed by individuals of G2 and G3. CONCLUSION: The exposure to noise does not determine changes in the behavior of the ARL; the DL rises with the exposure to occupational noise; the DL is higher than the ARL in 10 to 25dB.

Estudo comparativo entre nível de desconforto e reflexo acústico em trabalhadores / Comparative study between the level of discomfort and the acoustic reflex in workers

TEMA: estudo comparativo do nível do desconforto e do limiar do reflexo acústico em trabalhadores. OBJETIVO: observar o comportamento auditivo por meio da avaliação da atividade da contração do músculo estapédio e do nível de desconforto em pessoas expostas e não expostas a ruído ocupacional, com intuito de identificar alguma influencia do ruído no comportamento da contração do músculo estapédio e na sensibilidade auditiva. MÉTODO: o estudo foi desenvolvido no Serviço Social da Indústria - SESI Ceará. Foram selecionados 103 adultos com audição normal, de ambos os sexos, na faixa etária de 18 a 45 anos distribuídos em três grupos: G1 com 41 adultos expostos a ruído que utilizavam EPIA, G2 com 32 adultos expostos a ruído que não utilizavam EPIA e G3 composto por 30 adultos não expostos. Os indivíduos foram submetidos à avaliação audiológica, tendo sido analisado o LRA e ND nas freqüências de 500Hz, 1000Hz, 2000Hz, 3000Hz, 4000Hz e WN. A análise estatística foi realizada por meio dos testes de Mann Whitney, Wilcoxon e Kruskal com nível de significância em 5 por cento. RESULTADOS: não houve diferença estatística significante entre os LRA obtidos nos três grupos, com valores médios de 93 a 103dBNA; o LRA foi significantemente menor que o ND, tendo valores médios para ND variando de 111 a 119dBNA no G1, de 113 a 120dBNA no G2 e 106 a 114dBNA no G3; o ND é maior nos indivíduos do grupo G1 seguidos pelos grupos G2 e G3. CONCLUSÕES: o ruído não determina alterações no comportamento do LRA; o ND é aumentado pela exposição ao ruído ocupacional; o ND é maior que o LRA de 10 a 25dB.