RESUMO
Orofacial pain is a highly prevalent clinical condition, yet difficult to control effectively with available drugs. Much attention is currently focused on the anti-inflammatory and antinociceptive properties of lectins. The purpose of this study was to evaluate the antinociceptive effect of frutalin (FTL) using rodent models of inflammatory and neuropathic orofacial pain. Acute pain was induced by formalin, glutamate or capsaicin (orofacial model) and hypertonic saline (corneal model). In one experiment, animals were pretreated with l-NAME and naloxone to investigate the mechanism of antinociception. The involvement of the lectin domain in the antinociceptive effect of FTL was verified by allowing the lectin to bind to its specific ligand. In another experiment, animals pretreated with FTL or saline were submitted to the temporomandibular joint formalin test. In yet another, animals were submitted to infraorbital nerve transection to induce chronic pain, followed by induction of thermal hypersensitivity using acetone. Motor activity was evaluated with the rotarod test. A molecular docking was performed using the TRPV1 channel. Pretreatment with FTL significantly reduced nociceptive behaviour associated with acute and neuropathic pain, especially at 0.5 mg/kg. Antinociception was effectively inhibited by l-NAME and d-galactose. In line with in vivo experiments, docking studies indicated that FTL may interact with TRPV1. Our results confirm the potential pharmacological relevance of FTL as an inhibitor of orofacial nociception in acute and chronic pain mediated by TRPA1, TRPV1 and TRPM8 receptor.
Assuntos
Analgésicos/uso terapêutico , Dor Facial/tratamento farmacológico , Galectinas/uso terapêutico , Dor Aguda/tratamento farmacológico , Dor Aguda/metabolismo , Analgésicos/isolamento & purificação , Animais , Artocarpus/química , Modelos Animais de Doenças , Dor Facial/metabolismo , Galectinas/isolamento & purificação , Camundongos , Simulação de Acoplamento Molecular , Neuralgia , Ratos Wistar , Canais de Cátion TRPM/metabolismo , Canais de Cátion TRPV/metabolismo , Canais de Potencial de Receptor Transitório/metabolismoRESUMO
The present study was designed to verify whether frutalin (FTL) affords gastroprotection against the ethanol-induced gastric damage and to examine the underlying mechanism(s). Gastric damage was induced by intragastric administration of 0.2 ml of ethanol (96%). Mice in groups were pretreated with FTL (0.25, 0.5 and 1 mg/kg; i.p.), cimetidine (100 mg/kg; p.o.), or vehicle (0.9% of NaCl, 10 mL/kg; p.o.), 30 min before ethanol administration. They were sacrificed 30 min later, the stomachs excised, and the mucosal lesion area (mm²) measured by planimetry. Gastroprotection was assessed in relation to inhibition of gastric lesion area. To study the gastroprotective mechanism(s), its relations to capsaicin-sensitive fibers, endogenous prostaglandins, nitric oxide, sulphydryls, ATP-sensitive potassium channels, adrenoceptors, opioid receptors and calcium channels were analyzed. Treatments effects on ethanol-associated oxidative stress markers GSH and MDA were measured in gastric tissue. FTL afforded a dose-unrelated gastroprotection against the ethanol damage. However, it failed to prevent the ethanol-induced changes in the levels of GSH and MDA. It was observed that the gastroprotection by FTL was greatly reduced in animals pretreated with capsazepine, indomethacin, L-NAME or glibenclamide. Considering the results, it is suggested that the FTL could probably be a good therapeutic agent for the development of new medicine for the treatment of gastric ulcer.
Assuntos
Antiulcerosos/uso terapêutico , Antioxidantes/uso terapêutico , Galectinas/uso terapêutico , Mucosa Gástrica/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Animais , Antiulcerosos/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Biomarcadores/metabolismo , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Cimetidina/uso terapêutico , Etanol , Galactose/metabolismo , Galectinas/farmacologia , Mucosa Gástrica/patologia , Glutationa/metabolismo , Glibureto/farmacologia , Indometacina/farmacologia , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos , NG-Nitroarginina Metil Éster/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismoRESUMO
Immune cell homoeostasis is attributed to multiple distinct safety valves that are interconnected and intervene at defined checkpoints of the life cycle of immunocytes to guarantee clonal expansion and functional inactivation of self-reactive potentially autoaggressive lymphocytes. Galectins, animal lectins defined by shared consensus amino acid sequence and affinity for beta-galactose containing oligosaccharides, are found on various cells of the immune system, and their expression is associated with the differentiation and activation status of these cells. Over the past few years, galectins have been implicated in the regulation of many aspects of T cell physiology such as cell activation, differentiation, and apoptosis. In addition, a growing body of experimental evidence indicates that galectins may play critical roles in the modulation of chronic inflammatory disorders, autoimmunity, and cancer. Given the increased interest of immunologists in this field, the growing body of information raised during the past few years and the potential use of galectins as novel anti-inflammatory agents or targets for immunosuppressive drugs, we will summarise recent advances on the role of galectins in different aspects of T cell physiology and their impact in the development and/or resolution of chronic inflammatory disorders, autoimmunity, and cancer.