RESUMO

In this study, a pharmacological approach, together with the paw pressure test, was used to investigate the role of dopamine and its receptors in the peripheral processing of the nociceptive response in mice. Initially, the administration of dopamine (5, 20, and 80 ng/paw) in the hind paw of male Swiss mice (30-40 g) promoted antinociceptive effects in a dose-dependent manner. This was considered a peripheral effect, as it did not produce changes in the nociceptive threshold of the contralateral paw. The D2, D3, and D4 dopamine receptor antagonists remoxipride (4 µg/paw), U99194 (16 µg/paw), and L-745,870 (16 µg/paw), respectively, reversed the dopamine-mediated antinociception in mice with PGE2-induced hyperalgesia. The D1 and D5 dopamine receptor antagonists SKF 83566 (2 µg/paw) and SCH 23390 (1.6 µg/paw), respectively, did not alter dopamine antinociception. In contrast, dopamine at higher doses (0.1, 1, and 10 µg/paw) caused hyperalgesia in the animals, and the D1 and D5 receptor antagonists reversed this pronociceptive effect (10 µg/paw), whereas the D2 receptor antagonist remoxipride did not. Our data suggest that dopamine has a dual effect that depends on the dose, as it causes peripheral antinociceptive effects at small doses via the activation of D2-like receptors and nociceptive effects at higher doses via the activation of D1-like receptors.

Assuntos

RESUMO

Kahweol is a compound derived from coffee with reported antinociceptive effects. Based on the few reports that exist in the literature regarding the mechanisms involved in kahweol-induced peripheral antinociceptive action, this study proposed to investigate the contribution of the endocannabinoid system to the peripheral antinociception induced in rats by kahweol. Hyperalgesia was induced by intraplantar injection of prostaglandin E2(PGE2) and was measured with the paw pressure test. Kahweol and the drugs to test the cannabinoid system were administered locally into the right hind paw. The endocannabinoids were purified by open-bed chromatography on silica and measured by LC-MS. Kahweol (80 µg/paw) induced peripheral antinociception against PGE2-induced hyperalgesia. This effect was reversed by the intraplantar injection of the CB1 cannabinoid receptor antagonist AM251 (20, 40, and 80 µg/paw), but not by the CB2 cannabinoid receptor antagonist AM630 (100 µg/paw). Treatment with the endocannabinoid reuptake inhibitor VDM11 (2.5 µg/paw) intensified the peripheral antinociceptive effect induced by low-dose kahweol (40 µg/paw). The monoacylglycerol lipase (MAGL) inhibitor, JZL184 (4 µg/paw), and the dual MAGL/fatty acid amide hydrolase (FAAH) inhibitor, MAFP (0.5 µg/paw), potentiated the peripheral antinociceptive effect of low-dose kahweol. Furthermore, kahweol increased the levels of the endocannabinoid anandamide, but not of the other endocannabinoid 2-arachidonoylglycerol nor of anandamide-related N-acylethanolamines, in the plantar surface of the rat paw. Our results suggested that kahweol induced peripheral antinociception via anandamide release and activation of CB1 cannabinoid receptors and this compound could be used to develop new drugs for pain relief.

Assuntos

RESUMO

Recently, fish byproducts have been appraised as a source of structurally diverse bioactive compounds. In this context, fish mucus has revealed a myriad of pharmacological activities. This study describes a new bioactive molecule release system composed of protein nanoparticles from pacamã (Lophiosilurus alexandri) mucus, an endemic fish to the São Francisco River (Brazil). The process of obtaining and applying these nanoparticles, composed of proteins present in the pacamã mucus, as biocompatible carriers of bioactive molecules is also addressed herein. Therefore, the external mucus of the fish was collected, lyophilized and hydrated in deionized water containing the template molecule. After pH adjustment to 7.5, followed by sonication and centrifugation, the formed nanoparticles were collected in the supernatant. Additionally, the mucus and the particles were characterized, and pharmacological effects were evaluated regarding their antifungal, antibacterial, anticancer, anti or pro-inflammatory and antinociceptive proprieties. NP-Mucus did not exhibit antibacterial activity against Pseudomonas aeruginosa or Staphylococcus aureus. However, it showed potential effects against Candida albicans with a minimum inhibitory concentration (MIC) of 1 µg/mL, and significant pro-inflammatory role, reflected by cellular recruitment activity and healing effects. Therefore, future studies are now needed in order to identify specific compounds in NP-mucus responsible for the observed effects in order to provide new pharmacological and therapeutic strategies.(AU)

Recentemente, os subprodutos de peixes foram avaliados como uma fonte de compostos bioativos estruturalmente diversos. Nesse contexto, o muco dos peixes revelou uma miríade de atividades farmacológicas. Este estudo descreve um novo sistema de liberação de moléculas bioativas compostas por nanopartículas de proteínas do muco do pacamã (Lophiosilurus alexandri), um peixe do Rio São Francisco (Brasil). O processo de obtenção e aplicação dessas nanopartículas, compostas por proteínas presentes no muco do pacamã, como carreadores biocompatíveis de moléculas bioativas também são abordados neste artigo. Para tanto, o muco externo dos peixes foi coletado, liofilizado e hidratado em água deionizada contendo a molécula template. Após ajuste do pH para 7,5, seguido de sonicação e centrifugação, as nanopartículas formadas foram coletadas no sobrenadante. Adicionalmente, foram caracterizados o muco e as partículas, sendo avaliados os efeitos farmacológicos quanto às propriedades antifúngicas, antibacterianas, anticancerígenas, anti ou pró-inflamatórias e antinociceptivas. NP-Mucus não exibiu atividade antibacteriana contra Pseudomonas aeruginosa ou Staphylococcus aureus. No entanto, apresentou efeitos potenciais contra Candida albicans com concentração inibitória mínima (MIC) de 1 µg/mL, além de importante papel próinflamatório, refletido pela atividade de recrutamento celular e efeitos cicatrizantes. Portanto, estudos são necessários para identificar compostos no NP-muco responsáveis pelos efeitos observados, a fim de fornecer novas estratégias farmacológicas e terapêuticas.(AU)

Assuntos

RESUMO

Recently, fish byproducts have been appraised as a source of structurally diverse bioactive compounds. In this context, fish mucus has revealed a myriad of pharmacological activities. This study describes a new bioactive molecule release system composed of protein nanoparticles from pacamã (Lophiosilurus alexandri) mucus, an endemic fish to the São Francisco River (Brazil). The process of obtaining and applying these nanoparticles, composed of proteins present in the pacamã mucus, as biocompatible carriers of bioactive molecules is also addressed herein. Therefore, the external mucus of the fish was collected, lyophilized and hydrated in deionized water containing the template molecule. After pH adjustment to 7.5, followed by sonication and centrifugation, the formed nanoparticles were collected in the supernatant. Additionally, the mucus and the particles were characterized, and pharmacological effects were evaluated regarding their antifungal, antibacterial, anticancer, anti or pro-inflammatory and antinociceptive proprieties. NP-Mucus did not exhibit antibacterial activity against Pseudomonas aeruginosa or Staphylococcus aureus. However, it showed potential effects against Candida albicans with a minimum inhibitory concentration (MIC) of 1 µg/mL, and significant pro-inflammatory role, reflected by cellular recruitment activity and healing effects. Therefore, future studies a

RESUMO

Dipyrone (metamizole) is well-known for its powerful effect with central and peripheral activity. This meta-analysis involved articles published between 1973 and 2021, revealing that Brazil is the country which most published scientific articles relating the use of dipyrone in dogs, and this drug is widely recommended as an analgesic to control pain in cases of postoperative and cancer. Dipyrone is one of the favorite drugs used in small animal clinic in Brazil, and 12 commercial brands are available to use in dogs at doses among 25 to 50mg/kg for oral, intravenous and intramuscular administration. The effects of dipyrone may be potentiated when used in combination with other analgesic agents such as tramadol. In several studies, the occurrence of vomiting has been observed as an adverse effect, especially when the drug is used during surgical procedures, but metamizole has presented a low potential to cause gastric ulceration. The meta-analysis study of the use of dipyrone in dogs shows the clinical importance of this drug in Brazil, being an effective and safe medication, as long as it is used in the indicated dose of 25 mg/kg.

RESUMO

Dipyrone (metamizole) is well-known for its powerful effect with central and peripheral activity. This meta-analysis involved articles published between 1973 and 2021, revealing that Brazil is the country which most published scientific articles relating the use of dipyrone in dogs, and this drug is widely recommended as an analgesic to control pain in cases of postoperative and cancer. Dipyrone is one of the favorite drugs used in small animal clinic in Brazil, and 12 commercial brands are available to use in dogs at doses among 25 to 50mg/kg for oral, intravenous and intramuscular administration. The effects of dipyrone may be potentiated when used in combination with other analgesic agents such as tramadol. In several studies, the occurrence of vomiting has been observed as an adverse effect, especially when the drug is used during surgical procedures, but metamizole has presented a low potential to cause gastric ulceration. The meta-analysis study of the use of dipyrone in dogs shows the clinical importance of this drug in Brazil, being an effective and safe medication, as long as it is used in the indicated dose of 25 mg/kg.

A dipirona (metamizol) é bem conhecida por seu poderoso efeito com atividade central e periférica. Esta meta-nálise envolveu estudos publicados entre os anos de 1973 a 2021, revelando que o Brasil é o país que mais publicou artigos científicos envolvendo o uso de dipirona em cães, sendo este fármaco amplamente recomendado como analgésico para controlar a dor em casos de câncer e dor pós-operatória. É um dos medicamentos preferidos da clínica médica de pequenos animais no Brasil. 12 marcas comerciais estão disponíveis para uso em cães em doses que variam de 25 a 50g para administração oral, intravenosa e intramuscular. Os efeitos da dipirona podem ser potencializados quando usada em combinação com outros analgésicos, como o tramadol. Em vários estudos, a ocorrência de vômito tem sido observada como efeito adverso, principalmente quando o medicamento é usado durante procedimentos cirúrgicos, mas tem baixo potencial para causar ulceração gástrica. O estudo de meta-análise do uso de dipirona em cães evidencia a importância do uso clínico deste fármaco no Brasil, sendo um medicamento eficaz e seguro para cães, desde que utilizada na dose indicada de 25 mg / kg.

Assuntos

RESUMO

Recently, fish byproducts have been appraised as a source of structurally diverse bioactive compounds. In this context, fish mucus has revealed a myriad of pharmacological activities. This study describes a new bioactive molecule release system composed of protein nanoparticles from pacamã (Lophiosilurus alexandri) mucus, an endemic fish to the São Francisco River (Brazil). The process of obtaining and applying these nanoparticles, composed of proteins present in the pacamã mucus, as biocompatible carriers of bioactive molecules is also addressed herein. Therefore, the external mucus of the fish was collected, lyophilized and hydrated in deionized water containing the template molecule. After pH adjustment to 7.5, followed by sonication and centrifugation, the formed nanoparticles were collected in the supernatant. Additionally, the mucus and the particles were characterized, and pharmacological effects were evaluated regarding their antifungal, antibacterial, anticancer, anti or pro-inflammatory and antinociceptive proprieties. NP-Mucus did not exhibit antibacterial activity against Pseudomonas aeruginosa or Staphylococcus aureus. However, it showed potential effects against Candida albicans with a minimum inhibitory concentration (MIC) of 1 µg/mL, and significant pro-inflammatory role, reflected by cellular recruitment activity and healing effects. Therefore, future studies are now needed in order to identify specific compounds in NP-mucus responsible for the observed effects in order to provide new pharmacological and therapeutic strategies.

Recentemente, os subprodutos de peixes foram avaliados como uma fonte de compostos bioativos estruturalmente diversos. Nesse contexto, o muco dos peixes revelou uma miríade de atividades farmacológicas. Este estudo descreve um novo sistema de liberação de moléculas bioativas compostas por nanopartículas de proteínas do muco do pacamã (Lophiosilurus alexandri), um peixe do Rio São Francisco (Brasil). O processo de obtenção e aplicação dessas nanopartículas, compostas por proteínas presentes no muco do pacamã, como carreadores biocompatíveis de moléculas bioativas também são abordados neste artigo. Para tanto, o muco externo dos peixes foi coletado, liofilizado e hidratado em água deionizada contendo a molécula template. Após ajuste do pH para 7,5, seguido de sonicação e centrifugação, as nanopartículas formadas foram coletadas no sobrenadante. Adicionalmente, foram caracterizados o muco e as partículas, sendo avaliados os efeitos farmacológicos quanto às propriedades antifúngicas, antibacterianas, anticancerígenas, anti ou pró-inflamatórias e antinociceptivas. NP-Mucus não exibiu atividade antibacteriana contra Pseudomonas aeruginosa ou Staphylococcus aureus. No entanto, apresentou efeitos potenciais contra Candida albicans com concentração inibitória mínima (MIC) de 1 µg/mL, além de importante papel próinflamatório, refletido pela atividade de recrutamento celular e efeitos cicatrizantes. Portanto, estudos são necessários para identificar compostos no NP-muco responsáveis pelos efeitos observados, a fim de fornecer novas estratégias farmacológicas e terapêuticas.

Assuntos

RESUMO

Dipyrone (metamizole) is well-known for its powerful effect with central and peripheral activity. This meta-analysis involved articles published between 1973 and 2021, revealing that Brazil is the country which most published scientific articles relating the use of dipyrone in dogs, and this drug is widely recommended as an analgesic to control pain in cases of postoperative and cancer. Dipyrone is one of the favorite drugs used in small animal clinic in Brazil, and 12 commercial brands are available to use in dogs at doses among 25 to 50mg/kg for oral, intravenous and intramuscular administration. The effects of dipyrone may be potentiated when used in combination with other analgesic agents such as tramadol. In several studies, the occurrence of vomiting has been observed as an adverse effect, especially when the drug is used during surgical procedures, but metamizole has presented a low potential to cause gastric ulceration. The meta-analysis study of the use of dipyrone in dogs shows the clinical importance of this drug in Brazil, being an effective and safe medication, as long as it is used in the indicated dose of 25 mg/kg.(AU)

A dipirona (metamizol) é bem conhecida por seu poderoso efeito com atividade central e periférica. Esta meta-nálise envolveu estudos publicados entre os anos de 1973 a 2021, revelando que o Brasil é o país que mais publicou artigos científicos envolvendo o uso de dipirona em cães, sendo este fármaco amplamente recomendado como analgésico para controlar a dor em casos de câncer e dor pós-operatória. É um dos medicamentos preferidos da clínica médica de pequenos animais no Brasil. 12 marcas comerciais estão disponíveis para uso em cães em doses que variam de 25 a 50g para administração oral, intravenosa e intramuscular. Os efeitos da dipirona podem ser potencializados quando usada em combinação com outros analgésicos, como o tramadol. Em vários estudos, a ocorrência de vômito tem sido observada como efeito adverso, principalmente quando o medicamento é usado durante procedimentos cirúrgicos, mas tem baixo potencial para causar ulceração gástrica. O estudo de meta-análise do uso de dipirona em cães evidencia a importância do uso clínico deste fármaco no Brasil, sendo um medicamento eficaz e seguro para cães, desde que utilizada na dose indicada de 25 mg / kg.(AU)

Assuntos

RESUMO

Kahweol is a compound derived from coffee with reported antinociceptive effects. Based on the few reports that exist in the literature regarding the mechanisms involved in kahweol-induced peripheral antinociceptive action, this study proposed to investigate the contribution of the endocannabinoid system to the peripheral antinociception induced in rats by kahweol. Hyperalgesia was induced by intraplantar injection of prostaglandin E2(PGE2) and was measured with the paw pressure test. Kahweol and the drugs to test the cannabinoid system were administered locally into the right hind paw. The endocannabinoids were purified by open-bed chromatography on silica and measured by LC-MS. Kahweol (80 µg/paw) induced peripheral antinociception against PGE2-induced hyperalgesia. This effect was reversed by the intraplantar injection of the CB1 cannabinoid receptor antagonist AM251 (20, 40, and 80 μg/paw), but not by the CB2 cannabinoid receptor antagonist AM630 (100 μg/paw). Treatment with the endocannabinoid reuptake inhibitor VDM11 (2.5 μg/paw) intensified the peripheral antinociceptive effect induced by low-dose kahweol (40 μg/paw). The monoacylglycerol lipase (MAGL) inhibitor, JZL184 (4 μg/paw), and the dual MAGL/fatty acid amide hydrolase (FAAH) inhibitor, MAFP (0.5 μg/paw), potentiated the peripheral antinociceptive effect of low-dose kahweol. Furthermore, kahweol increased the levels of the endocannabinoid anandamide, but not of the other endocannabinoid 2-arachidonoylglycerol nor of anandamide-related N-acylethanolamines, in the plantar surface of the rat paw. Our results suggested that kahweol induced peripheral antinociception via anandamide release and activation of CB1 cannabinoid receptors and this compound could be used to develop new drugs for pain relief.

RESUMO

Establishing new animal models for the study of inflammation is very important in the process of discovering new drugs, since the inflammatory event is the basis of many pathological processes. Whereas rodent models have been the primary focus of inflammation research, we defend the zebrafish (Danio rerio) test as a feasible alternative for preclinical studies. Moreover, despite all the technological development already achieved by humanity, nature can still be considered a relevant source of new medicines. In this context, the aim of this work was to evaluate the anti-inflammatory effect of a substance isolated from the medicinal plant Annona crassilfora Mart, the peltatoside, in an inflammatory model of zebrafish. It was determined: (i) total leukocyte count in the coelomate exudate; (ii) N-acetyl-ß-d-glucuronidase (NAG); (iii) myeloperoxidase (MPO); (iv) and the histology of liver, intestine and mesentery. Peltotoside (25, 50 and 100 µg) and dexamethasone (25 µg) were administered intracelomatically (i.c.) 30 min before carrageenan (i.c.). Pretreatment with peltatoside at three doses significantly inhibited leukocyte recruitment in the coelomic cavity, and inhibited NAG and MPO activity against the action of Cg, in a similar manner as dexamethasone. However, some microlesions in the evaluated organs were detected. The dose of 25 µg showed an anti-inflammatory effect with lower undesirable effects in the tissues. Our results suggest that the zebrafish test was satisfactory in performing our analyzes and that the peltotoside has a modulatory action in reducing leukocyte migration.

Assuntos