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1.
Adv Rheumatol ; 62(1): 42, 2022 11 12.
Article En | MEDLINE | ID: mdl-36371322

OBJECTIVE: To describe parametric changes observed using scanning electron microscopy (SEM) in very early stages in posttraumatic osteoarthritis (OA) models in mice. METHODS: Mice (5/group) had their knees subjected to anterior cruciate ligament transection (ACLT), ACLT plus meniscectomy (MNCT) or sham surgery, sacrificed after 3, 7 or 14 days, had the articular cartilage evaluated under optical microscopy using Osteoarthritis Research Society International (OARSI) parameters as well as cartilage thickness, roughness, and a damage index using SEM. RESULTS: Alterations of the cartilage under optical microscopy were not significantly relevant among groups. SEM analysis revealed reduction of femoral and tibial cartilage thickness in ACLT and MNCT groups at 7 and 14 days, with increased cartilage roughness in MNCT group as early as 3 days postsurgery, being sustained up to 14 days. Articular damage index was significantly higher at 14 days post surgery in ACLT and MNCT vs control groups. CONCLUSION: This is the first demonstration of very early quantitative changes in the cartilage of mice subjected to posttraumatic experimental OA using SEM, revealing increased roughness and thickness as early as 3 days post surgery. These changes may be used as early surrogates for later joint damage in experimental OA.


Cartilage, Articular , Osteoarthritis , Mice , Humans , Animals , Microscopy, Electron, Scanning , Disease Models, Animal , Osteoarthritis/diagnostic imaging , Cartilage, Articular/diagnostic imaging , Anterior Cruciate Ligament/surgery
2.
Front Neurosci ; 16: 742239, 2022.
Article En | MEDLINE | ID: mdl-35546897

Objective: Moringa oleifera possesses multiple biological effects and the 4-[(4'-O-acetyl-α-L- rhamnosyloxy) benzyl] isothiocyanate accounts for them. Based on the original isothiocyanate molecule we obtained a semisynthetic derivative, named 4-[(2',3',4'-O-triacetyl-α-L-rhamnosyloxy) N-benzyl] hydrazine carbothioamide (MC-H) which was safe and effective in a temporomandibular joint (TMJ) inflammatory hypernociception in rats. Therefore, considering that there is still a gap in the knowledge concerning the mechanisms of action through which the MC-H effects are mediated, this study aimed to investigate the involvement of the adhesion molecules (ICAM-1, CD55), the pathways heme oxygenase-1 (HO-1) and NO/cGMP/PKG/K+ ATP, and the central opioid receptors in the efficacy of the MC-H in a pre-clinical study of TMJ pain. Methods: Molecular docking studies were performed to test the binding performance of MC-H against the ten targets of interest (ICAM-1, CD55, HO-1, iNOS, soluble cGMP, cGMP-dependent protein kinase (PKG), K+ ATP channel, mu (µ), kappa (κ), and delta (δ) opioid receptors). In in vivo studies, male Wistar rats were treated with MC-H 1 µg/kg before TMJ formalin injection and nociception was evaluated. Periarticular tissues were removed to assess ICAM-1 and CD55 protein levels by Western blotting. To investigate the role of HO-1 and NO/cGMP/PKG/K+ ATP pathways, the inhibitors ZnPP-IX, aminoguanidine, ODQ, KT5823, or glibenclamide were used. To study the involvement of opioid receptors, rats were pre-treated (15 min) with an intrathecal injection of non-selective inhibitor naloxone or with CTOP, naltrindole, or norbinaltorphimine. Results: All interactions presented acceptable binding energy values (below -6.0 kcal/mol) which suggest MC-H might strongly bind to its molecular targets. MC-H reduced the protein levels of ICAM-1 and CD55 in periarticular tissues. ZnPP-IX, naloxone, CTOP, and naltrindole reversed the antinociceptive effect of MC-H. Conclusion: MC-H demonstrated antinociceptive and anti-inflammatory effects peripherally by the activation of the HO-1 pathway, as well as through inhibition of the protein levels of adhesion molecules, and centrally by µ and δ opioid receptors.

3.
J Oral Biol Craniofac Res ; 10(3): 276-280, 2020.
Article En | MEDLINE | ID: mdl-32518744

OBJECTIVE: Chresta martii is broadly used by folk medicine due to its anti-inflammatory effects, but there is a lack of preclinical data on its pharmacological mechanisms. This study investigated the efficacy of Chresta martii ethanolic extract (CEE) in the zymosan-induced temporomandibular joint arthritis (TMJ) and evaluated the possible role of TNF-α, nitric oxide (NO), and heme oxygenase-1 (HO-1). METHODS: Male Wistar rats (160-220 g) were pre-treated with CEE (100, 200 or 400 mg/kg; v.o) 1 h before zymosan injection (2 mg; i.art). Mechanical hypernociception (g) was assessed 4 h later. The trigeminal ganglion was collected for TNF-α quantification (ELISA), total cell count and myeloperoxidase activity (MPO) were assayed in the synovial lavage 6 h after arthritis induction. Additionally, animals were pre-treated with L-NAME (30 mg/kg; i.p.) or ZnPP-IX (3 mg/kg, s.c.) to assess the involvement of NO and HO-1, respectively. RESULTS: CEE 400 mg/kg (v.o) increased (p < 0.05) hypernociception threshold, reduced the cell counts and MPO activity in the synovial lavage, as well as decreased TNF-α levels in the trigeminal ganglion. ZnPP-IX abolished the analgesic effect of CEE, but not L-NAME. CONCLUSION: The anti-inflammatory and antinociceptive effects of CEE depended on the HO-1 pathway integrity and TNF-α suppression.

4.
Int J Biol Macromol ; 150: 253-260, 2020 May 01.
Article En | MEDLINE | ID: mdl-32004610

Temporomandibular disorder is a clinical painful condition in the temporomandibular joint (TMJ) region. The purified sulfated polysaccharide from the green marine algae Caulerpa racemosa (Cr) has provided anti-inflammatory and antinociceptive activity. This study evaluated these effects on a TMJ hypernociception model. Wistar rats (180 - 250 g) were pre-treated (i.v.) with Cr at 0.01, 0.1, or 1 mg/kg or vehicle 30 min before formalin (1.5%/50 µL, i.art.), capsaicin (1.5%/20 µL, i.art.), or serotonin (225 µg/50 µL, i.art.) in the TMJ, and nociceptive behaviors were measured for 45 or 30 min upon inflammatory stimuli. Inflammatory parameters vascular permeability assay, TNF-α, and IL-1ß by ELISA, protein expression of adhesion molecules ICAM-1 and CD55 by Western blot were assessed. The involvement of heme oxygenase-1 (HO-1) and nitric oxide (NO) pathways were assessed by pharmacological inhibition. Cr (1 mg/kg) reduced nociceptive behavior, plasmatic extravasation, TNF-α, and IL-1ß levels, as well as ICAM-1 and CD55 expression in periarticular tissues. Cr antinociceptive effect was not prevented by aminoguanidine, but ZnPP-IX did reduce its antinociceptive effect. Therefore, Cr antinociceptive and anti-inflammatory effects in this experimental model of hypernociception depended on the HO-1 pathway integrity, as well as reducing peripheral inflammatory events, e.g., TNF-α and IL-1ß cytokines levels, ICAM-1 and CD55 expression.


Analgesics/chemistry , Analgesics/pharmacology , Aquatic Organisms/chemistry , Chlorophyta/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Sulfates/chemistry , Animals , Arthralgia/drug therapy , Arthralgia/etiology , Arthralgia/metabolism , Biomarkers , Capsaicin/adverse effects , Cytokines/metabolism , Heme Oxygenase-1/metabolism , Inflammation Mediators/metabolism , Male , Nitric Oxide/metabolism , Rats , Temporomandibular Joint/drug effects , Temporomandibular Joint/physiopathology
5.
Curr Pharm Des ; 25(12): 1430-1439, 2019.
Article En | MEDLINE | ID: mdl-31124421

ETHNOPHARMACOLOGICAL RELEVANCE: Mucuna pruriens (Mp) belongs to Leguminosae family, it is native of tropical regions and used to treat several maladies such as urinary, neurological, and menstruation disorders, constipation, edema, fever, tuberculosis, ulcers, diabetes, arthritis, dysentery, and cardiovascular diseases. Mp seeds are rich in bioactive compounds, for instance, lectins, a heterogeneous group of proteins and glycoproteins with a potential role as therapeutic tools for several conditions, including gastric disorders. This study investigated the acute toxicity, gastroprotective, and antioxidant activities of a lectin from Mucuna pruriens seeds (MpLec) on ethanol-induced gastropathy model in mice. MATERIAL AND METHODS: Mice received MpLec (5 or 10 mg/kg; i.v.) and were observed for acute toxicity signs; in another experimental series, mice were pre-treated with MpLec (0.001; 0.01 or 0.1 mg/kg, i.v.), ranitidine (80 mg/kg, p.o.), or saline (0.3 mL/30g, i.v.) before ethanol 99.9% (0.2 mL/animal, p.o.), and euthanized 30 min after ethanol challenge. Macroscopic and microscopic gastric aspects, biochemical parameters (tissue hemoglobin levels, iron-induced lipid peroxidation, GSH content, SOD activity, and gastric mucosal PGE2) were measured. Additionally, pharmacological tools (yohimbine, indomethacin, naloxone, L-NAME) were opportunely used to clarify MpLec gastroprotective mechanisms of action. RESULTS: No toxicity signs nor death were observed at acute toxicity tests. MpLec reduced ethanol-induced gastric damage, edema, and hemorrhagic patches formation, as well as decreased lipid peroxidation, SOD activity, and increased GSH content. Yohimbine and indomethacin prevented MpLec effects, suggesting the involvement of alpha-2 adrenoceptors and prostaglandins in the MpLec-mediated effects. CONCLUSION: MpLec does not present toxicity signs and shows gastroprotective and antioxidant activities via alpha-2 adrenoceptors and prostaglandins in the ethanol-induced gastropathy model.


Antioxidants/pharmacology , Gastric Mucosa/drug effects , Lectins/pharmacology , Mucuna/chemistry , Prostaglandins/metabolism , Receptors, Adrenergic/metabolism , Stomach Ulcer/therapy , Animals , Ethanol/adverse effects , Lipid Peroxidation , Mice , Phytotherapy , Plant Extracts/therapeutic use , Seeds/chemistry , Stomach Ulcer/chemically induced , Toxicity Tests, Acute
6.
Int J Biol Macromol ; 125: 53-60, 2019 Mar 15.
Article En | MEDLINE | ID: mdl-30500503

Lonchocarpus campestris (tribe Dalbergieae) possess a mannose biding lectin (LCaL) purified by ion exchange chromatography on DEAE-Sephacel, HiTrap DEAE FF and TSKgel engaged in AKTA-HPLC system. LCaL agglutinates trypsinized rabbit erythrocytes and its activity was maintained after incubation in a wide range of temperature (4-100 °C) and pH (4-9). The lectin had its apparent molecular weight evaluated by size-exclusion chromatography and SDS-PAGE and presented a profile of 10 kDa and 25 kDa in denaturing and native conditions, respectively. LCaL injected by intravenous route in mice showed antinociceptive activity in the behavioral tests of Formalin and Writhing. In the formalin test LCaL inhibited the licking time by 37% in the neurogenic phase and by 73% in the inflammatory phase. In the acetic acid-induced writhing test LCaL showed inhibitory effect at 0.1 mg/kg (72%), 1 mg/kg (74%) and 10 mg/kg (70%). The lectin also inhibited the increase in vascular permeability at 10 mg/kg and leukocyte migration at 0.1, 1 and 10 mg/kg concentrations. Additionally, LCaL inhibited paw edema (mainly from 1 to 3 h by 46%) and hyperalgesia (1 h: 82%; 3 h: 63%) induced by carrageenan. In conclusion, LCaL presents an antinociceptive action mainly via inhibition of inflammation.


Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Fabaceae/chemistry , Lectins/isolation & purification , Nociception/drug effects , Seeds/chemistry , Animals , Hemagglutination , Lectins/chemistry , Male , Mice , Molecular Weight
7.
Chem Biol Interact ; 294: 118-127, 2018 Oct 01.
Article En | MEDLINE | ID: mdl-30107152

Chemo-resistance has been reported as a relevant barrier for the efficiency of gastric cancer treatment. Therefore, the development of effective and safe drugs for cancer chemotherapy is still a challenge. The purpose of this study was to evaluate the anticancer potential of (E)-2-(((2-(benzo[d]thiazo-2-yl)hydrazono)methyl)-4-nitrophenol) (AFN01) against gastric cancer cell lines. Our results showed promising anticancer activity against gastric cancer cells ACP-02 (IC50 = 1.0 µM) and mild activity against other cell lines including non-malignant gastric cell MNP-01 (IC50 = 3.4 µM). This compound significantly induced S phase cell cycle arrest, prevented cell migration and triggered apoptosis in a concentration-dependent manner. Moreover, AFN01 was significantly more genotoxic against tumoral cell ACP-02, when compared to non-malignant cells, such as MNP-01 and healthy peripheral mononuclear blood cells. AFN01 also synergistically interacts with doxorubicin suppressing cell proliferation and c-MYC gene expression in gastric cancer cell line model, with remarkable c-MYC overexpression. Although further pre-clinical and clinical studies are required to explore its safety and efficiency, AFN01 may represent a promising lead anticancer agent for the treatment of gastric cancer.


Apoptosis/drug effects , Benzothiazoles/pharmacology , DNA/metabolism , Proto-Oncogene Proteins c-myc/metabolism , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Benzothiazoles/chemistry , Caspase 3/metabolism , Caspase 7/metabolism , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , DNA/chemistry , Down-Regulation/drug effects , Humans , Proto-Oncogene Proteins c-myc/genetics , Stereoisomerism , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology
8.
Int J Biol Macromol ; 115: 331-340, 2018 Aug.
Article En | MEDLINE | ID: mdl-29660457

Temporomandibular disorders are the second most common cause of orofacial pain mediated by inflammatory compounds, which in many cases leads to chronic orofacial pain. This study assessed the antinociceptive and anti-inflammatory effects of a lectin from the green seaweed Caulerpa cupressoides (CcL) on hypernociception inflammatory in TMJ of rats and investigated the involvement of different mechanisms. Rats received i.v. CcL 30 min prior to injection of flogistic agentes or 0.9% saline into the left TMJ. Pretreatment with CcL (0. 1; 1 or 10 mg/kg) promoted a reduction (p < 0.05) of inflammatory hypernociception induced by 1.5% Formalin along with inhibition of inflammatory plasma extravasation, cytokines levels, ciclooxigenase-2, and intercellular adhesion molecule (ICAM-1). CcL was able to inhibit the nociceptive response induced by 1.5% Capsaicin, suggesting that CcL has an antinociceptive effect, acting directly on the primary nociceptive neurons. CcL also inhibited the nociceptive response induced by Carrageenan (100 µg/TMJ) or Serotonin (5-HT) (225 µg/TMJ). In conclusion, the results demonstrate that administration of CcL has a potential antinociceptive and anti-inflammatory effect, with a mechanism that is partially dependent on TNF-α, IL-1ß, COX-2 and ICAM-1 inhibition and independently from the cannabinoide and opioid system and NO/cGMP/PKG/K+ATP channel pathway.


Analgesics/pharmacology , Caulerpa/chemistry , Plant Lectins/pharmacology , Temporomandibular Joint/drug effects , Animals , Cell Adhesion Molecules/metabolism , Cyclooxygenase 2/metabolism , Inflammation/physiopathology , Interleukin-1beta/biosynthesis , Male , Motor Activity/drug effects , Nociception/drug effects , Rats , Rats, Wistar , Temporomandibular Joint/metabolism , Tumor Necrosis Factor-alpha/biosynthesis
9.
Biomed Pharmacother ; 98: 863-872, 2018 Feb.
Article En | MEDLINE | ID: mdl-29571257

Tocoyena sellowiana (Cham. & Schltdl.) K.Schum is one of the most important families of Brazilian medicinal plants. This study aimed to evaluate the effect of Tocoyena sellowiana (Cham. & Schltdl.) K.Schum ethanolic extract in a pre-clinical trial of periodontitis and to investigate possible mechanisms underlying such effects. Periodontitis was induced in Wistar rats by placing a nylon thread ligature around second upper left molars for 11 days. Rats received (per os) Tocoyena sellowiana (0.1, 1 or 10?mg?kg) or vehicle 1?h before ligature and daily until day 11. Macroscopic, histopathological, and COX-2 immunohistochemical analyses were performed to evaluate the periodontium. The gingival tissue was used to quantify the myeloperoxidase (MPO) activity and interleukin (IL)-1? levels by ELISA. Blood samples were collected to evaluate bone-specific alkaline phosphatase (BALP), the dosage of creatinine, aspartate and alanine transaminases. The liver, kidneys, spleen, and body mass variations were also evaluated. Tocoyena sellowiana decreased bone loss, reduced MPO, IL-1? levels as well as COX-2 immunostaining, and increased BALP activity. Moreover, Tocoyena sellowiana did not alter organs nor body weight. Tocoyena sellowiana reduced bone loss in rats and its efficacy was at least partially dependent upon both IL-1? and cyclooxygenase-2 inhibition.


Alveolar Bone Loss/complications , Alveolar Bone Loss/drug therapy , Cyclooxygenase 2/metabolism , Interleukin-1beta/metabolism , Periodontitis/drug therapy , Plant Extracts/therapeutic use , Rubiaceae/chemistry , Alkaline Phosphatase/blood , Alveolar Bone Loss/blood , Alveolar Bone Loss/pathology , Animals , Dinoprostone/metabolism , Disease Models, Animal , Female , Gingiva/pathology , Organ Size/drug effects , Periodontitis/blood , Periodontitis/complications , Periodontitis/pathology , Peroxidase/metabolism , Phytotherapy , Plant Extracts/pharmacology , Rats, Wistar
10.
Biomed Pharmacother ; 101: 478-484, 2018 May.
Article En | MEDLINE | ID: mdl-29501769

Abelmoschus esculentus is largely cultivated in Northeastern Brazil for medicinal purposes, e.g. inflammatory conditions. This study aimed to evaluate the efficacy of Abelmoschus esculentus lectin (AEL) in reducing formalin-induced temporomandibular joint inflammatory hypernociception in rats. The behavioral experiments were performed in male Wistar rats (180-240 g). Rats were pre-treated (i.v.) with AEL (0.001, 0.01 or 0.1 mg/kg) 30 min before formalin injection (i.art.). To analyze the possible effect of opioid pathways on AEL efficacy, animals were pre-treated with naloxone or CTOP (µ opioid receptor antagonist), naltrindole (δ opioid receptor antagonist) or nor-binaltorphimine (κ opioid receptor antagonist) (i.t.) 15 min before AEL administration followed by intra-TMJ injection of 1.5% formalin. Animals were monitored for a 45-min observation period. TMJ tissue, trigeminal ganglion, and subnucleus caudalis were collected for TNF-α dosage (ELISA). In addition, the vascular permeability was evaluated by Evans Blue extravasation. AEL significantly reduced formalin-induced TMJ inflammatory hypernociception and decreased Evans blue extravasation. It decreased TNF-α levels in the TMJ tissue, trigeminal ganglion, and subnucleus caudalis. AEL antinociceptive effects were not observed in the presence of naltrindole or nor-binaltorphimine, suggesting that AEL efficacy depends on TNF-α inhibition and the activation of δ and κ opioid receptors. AEL has provided prominent analgesic and anti-inflammatory effects in this pre-clinical model of TMJ, supporting its possible use as a pharmacological tool for the management of painful conditions.


Abelmoschus/chemistry , Analgesics/pharmacology , Lectins/pharmacology , Pain/drug therapy , Receptors, Opioid/metabolism , Temporomandibular Joint/drug effects , Analgesics, Opioid/pharmacology , Animals , Anti-Inflammatory Agents/pharmacology , Formaldehyde/pharmacology , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/metabolism , Male , Overnutrition/drug therapy , Overnutrition/metabolism , Pain/chemically induced , Pain/metabolism , Rats , Rats, Wistar , Temporomandibular Joint/metabolism , Tumor Necrosis Factor-alpha/metabolism
11.
Biomed Pharmacother ; 98: 609-618, 2018 Feb.
Article En | MEDLINE | ID: mdl-29289835

Inflammation is a key component of many clinical conditions that affect the temporomandibular joint (TMJ) and Moringa oleifera Lam. has been used to treat inflammatory diseases. Here, we evaluated the toxicological effects on mice of a naturally-occurring isothiocyanate from M. oleifera and its seven analogue molecules. Further, the anti-nociceptive and anti-inflammatory effects on a rat model of TMJ inflammatory hypernociception were assessed. The systemic toxicological profile was determined in mice over a 14-day period: MC-1 1 µg/kg; MC-D1 1 µg/kg, MC-D3 100 µg/kg, MC-D6 1 µg/kg, MC-D7 1 µg/kg, MC-D8 1 µg/kg, MC-D9 10 µg/kg, and MC-H 1 µg/kg. The safest molecules were assayed for anti-nociceptive efficacy in the formalin (1.5%, 50 µL) and serotonin (255 mg) induced TMJ inflammatory hypernociception tests. The anti-inflammatory effect was evaluated through the vascular permeability assay using Evans blue. Further, the rota-rod test evaluated any motor impairment. Among the tested molecules, MC-D7, MC-D9, and MC-H were not toxic at the survival rate test, biochemical, and hystological analysis. They reduced the formalin-induced TMJ inflammatory hypernociception, but only MC-H decreased the serotonin-induced TMJ inflammation, suggesting an adrenergic receptor-dependent effect. They diminished the plasmatic extravasation, showing anti-inflammatory activity. At the rota-rod test, no difference was observed in comparison with control groups, reinforcing the hypothesis of anti-nociceptive effetc without motor impairment in animals. The analogues MC-D7, MC-D9, and MC-H were safe at the tested doses and efficient in reducing the formalin-induced TMJ hypernociception in rats. Our next steps include determining their mechanisms of anti-nociceptive action.


Analgesics/pharmacology , Anti-Inflammatory Agents/pharmacology , Inflammation/drug therapy , Isothiocyanates/chemistry , Moringa oleifera/adverse effects , Moringa oleifera/chemistry , Pain/drug therapy , Analgesics/adverse effects , Analgesics/chemistry , Animals , Anti-Inflammatory Agents/adverse effects , Anti-Inflammatory Agents/chemistry , Disease Models, Animal , Female , Inflammation/metabolism , Male , Mice , Pain/metabolism , Plant Extracts/adverse effects , Plant Extracts/chemistry , Plant Extracts/pharmacology , Rats , Rats, Wistar , Temporomandibular Joint/drug effects
12.
Inflamm Res ; 67(5): 407-422, 2018 May.
Article En | MEDLINE | ID: mdl-29362850

OBJECTIVE AND DESIGN: To investigate the role of heme oxygenase-1 (HO-1), carbon monoxide (CO), and biliverdin (BVD) in the zymosan-induced TMJ arthritis in rats. MATERIALS AND METHODS: Mechanical threshold was assessed before and 4 h after TMJ arthritis induction in rats. Cell influx, myeloperoxidase activity, and histological changes were measured in the TMJ lavages and tissues. Trigeminal ganglion and periarticular tissues were used for HO-1, TNF-α, and IL-1ß mRNA time course expression and immunohistochemical analyses. Hemin (0.1, 0.3, or 1 mg kg-1), DMDC (0.025, 0.25, or 2.5 µmol kg-1), biliverdin (1, 3, or 10 mg kg-1), or ZnPP-IX (1, 3 or 9 mg kg-1) were injected (s.c.) 60 min before zymosan. ODQ (12.5 µmol kg-1; s.c.) or glibenclamide (10 mg kg-1; i.p.) was administered 1 h and 30 min prior to DMDC (2.5 µmol kg-1; s.c), respectively. RESULTS: Hemin (1 mg kg-1), DMDC (2.5 µmol kg-1), and BVD (10 mg kg-1) reduced hypernociception and leukocyte migration, which ZnPP (3 mg kg-1) enhanced. The effects of DMDC were counteracted by ODQ and glibenclamide. The HO-1, TNF-α, and IL-1ß mRNA expression and immunolabelling increased. CONCLUSIONS: HO-1/BVD/CO pathway activation provides anti-nociceptive and anti-inflammatory effects on the zymosan-induced TMJ hypernociception in rats.


Biliverdine/physiology , Carbon Monoxide/physiology , Cyclic GMP , Heme Oxygenase-1/physiology , KATP Channels , Nociception/drug effects , Signal Transduction/drug effects , Animals , Arthritis/chemically induced , Biliverdine/genetics , Cytokines/metabolism , Down-Regulation/drug effects , Heme Oxygenase-1/genetics , Male , Pain Threshold , Peroxidase/metabolism , Potassium Channel Blockers/pharmacology , Rats , Rats, Wistar , Temporomandibular Joint Disorders/chemically induced , Temporomandibular Joint Disorders/pathology , Trigeminal Ganglion/drug effects , Zymosan
13.
J Oral Maxillofac Res ; 9(4): e4, 2018.
Article En | MEDLINE | ID: mdl-30746053

OBJECTIVES: The purpose of this study was to determine the effects of strontium ranelate on ligature-induced periodontitis in rats and assess the putative involvement of heme oxygenase-1 (HO-1) pathway in these effects. MATERIAL AND METHODS: Male Wistar rats underwent nylon ligature placement around maxillary molars and were treated (v.o.) with strontium ranelate (20 or 100 mg/kg) for 7 days. After that, rats were euthanized and histomorphometric/histopathological analyses and RT-PCR for HO-1 expression were performed. RESULTS: Strontium ranelate (20 or 100 mg/kg) prevented bone resorption by 28% and 38%, respectively. Strontium ranelate treatment (100 mg/kg) up-regulated (P < 0.05) heme oxygenase-1 mRNA levels in the gingival tissues in comparison to control groups. CONCLUSIONS: Strontium ranelate prevented periodontal bone loss in experimental periodontitis in rats while heme oxygenase-1 mRNA levels increased after treatment.

14.
Pharmacol Rep ; 69(4): 764-772, 2017 Aug.
Article En | MEDLINE | ID: mdl-28587937

BACKGROUND: Temporomandibular joint (TMJ) disorders show inflammatory components, heavily impacting on quality of life. Strontium ranelate has previously shown anti-inflammatory and antinociceptive effects on other experimental inflammatory pain models. Thus, we aim to investigate the strontium ranelate efficacy in reducing the zymosan-induced inflammatory hypernociception in the TMJ of rats by evaluating the TNF-α, IL-1ß, and hemeoxygenase-1 (HO-1) involvement. METHODS: Wistar rats were treated with strontium ranelate (0.5, 5 or 50 mg/kg, per os) 1 h before zymosan injection (iart). Mechanical threshold was assessed by Von Frey test and synovial lavage was collected for leukocyte counting and myeloperoxidase measurement, joint tissue and trigeminal ganglion were excised for histopathological analysis (H&E) and TNF-α/IL-1ß levels dosage (ELISA). Moreover, rats were pre-treated with ZnPP-IX (3 mg/kg, sc), a specific HO-1 inhibitor, before strontium ranelate administration (0.5 mg/kg, per os), and Evans Blue (5 mg/kg, iv) was administered to assess plasma extravasation. Pre-treatment with indomethacin (5 mg/kg, sc) was used as positive control while the sham group received 0.9% sterile saline (per os and iart). RESULTS: Strontium ranelate did not reduce leukocyte counting, myeloperoxidase activity, Evans Blue extravasation, IL-1ß levels, and TNF-α/IL-1ß immunolabeling; but it increased the nociceptive threshold and reduced TNF-α levels. Additionally, HO-1 inhibition did not change the strontium ranelate effects. CONCLUSION: Strontium ranelate may achieve its antinociceptive effects through the reduction of TNF-α levels in the trigeminal ganglion, but not suppressing IL-1ß expression nor inducing the HO-1 pathway.


Inflammation/drug therapy , Pain/drug therapy , Temporomandibular Joint Disorders/drug therapy , Thiophenes/pharmacology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Zymosan/toxicity , Animals , Drug Interactions , Enzyme-Linked Immunosorbent Assay , Interleukin-1beta , Male , Protoporphyrins/administration & dosage , Protoporphyrins/pharmacokinetics , Rats , Rats, Wistar , Thiophenes/pharmacokinetics
15.
Rev. bras. promoç. saúde (Impr.) ; 30(1): 13-21, 29/03/2017.
Article En, Es, Pt | LILACS | ID: biblio-846642

Objetivo: Analisar as atividades de Educação em Saúde realizadas pelas equipes de saúde bucal que estão inseridas na Estratégia Saúde da Família (ESF). Métodos: A pesquisa classificou-se em exploratória e descritiva, com abordagem qualitativa. O referencial teórico de Educação em Saúde utilizado foi a Educação Popular. O estudo foi realizado em Centros de Saúde da Família, Centro de Referência em Assistência Social (CRAS) e escolas no município de Sobral, Ceará, Brasil, entre os meses de novembro de 2013 e janeiro de 2014. Participaram do estudo 17 profissionais das equipes de saúde bucal. Os dados foram coletados por meio de entrevista contendo questões norteadoras e observação simples, sendo processados por meio da Análise do Discurso. Resultados: A concepção de Educação em Saúde referida majoritariamente pelos profissionais relaciona-se com o modelo tradicional. As atividades educativas realizadas não são sistematizadas para todo o município e estão condicionadas a programas ministeriais. A integração entre as equipes de saúde bucal e as equipes de saúde da família, no que diz respeito às atividades para escolares, é um processo ainda em construção, não estando consolidado na ESF. Conclusão: É necessário o desenvolvimento de políticas mais intensivas de formação de profissionais de saúde, que considerem a Educação Popular e o uso de metodologias ativas de ensino como método nas suas formações. Este estudo poderá contribuir para uma reflexão a respeito do tema na prática, podendo, assim, possibilitar a construção de um novo olhar sobre a Educação em Saúde.


Objective: To analyze the health education activities carried out by the oral health teams comprised in the Family Health Strategy (FHS). Methods: The research was classified as exploratory and descriptive, with a qualitative approach. Popular Education was adopted as the theoretical framework of Health Education. The study was performed at Family Health Centers, the Reference Center on Social Assistance (Centro de Referência em Assistência Social - CRAS) and schools in the municipality of Sobral, Ceará, Brazil, between November 2013 and January 2014. Seventeen professionals working in the oral health teams took part in the study. Data was collected through an interview with guiding questions and simple observation, and was processed through Discourse Analysis. Results: The conception of Health Education mostly referred to by the professionals is related to the traditional model. The educational activities carried out are not systematized for the whole municipality and are subject to ministerial programs. The integration between the oral health teams and the family health teams, with regard to activities for schoolchildren, is a process still under construction, not yet consolidated in the FHS. Conclusion: The development of more intensive policies for the training of health professionals, which consider Popular Education and the use of active teaching methodologies as method in their formation, is necessary. This study may contribute to a reflection regarding the theme in practice, thus enabling the construction of a new approach to Health Education.


Objetivo: Analizar las actividades de educación en salud realizadas por los equipos de salud bucal inseridas en la Estrategia Salud de la Familia (ESF). Métodos: Se clasificó la investigación en exploratoria y descriptiva de abordaje cualitativo. El referencial teórico de educación en salud utilizado fue lo de Educación Popular. El estudio fue realizado en Centros de Salud de la Familia, Centro de Referencia en Asistencia Social (CRAS) y escuelas del municipio de Sobral, Ceará, Brasil entre los meses de noviembre de 2013 y enero de 2014. Participaron del estudio 17 profesionales del Equipo de Salud Bucal. Se recogieron los datos a través de entrevista con preguntas norteadoras y observación simples siendo procesados a través del Análisis del Discurso. Resultados: La concepción de Educación en Salud relatada por la mayoría de los profesionales se relaciona con el Modelo Tradicional de Educación en Salud. Las actividades educativas realizadas no son sistematizadas para todo el municipio y dependen de los programas ministeriales. Respecto las actividades para los escolares, la integración entre el Equipo de Salud Bucal y el Equipo de Salud de la Familia es un proceso todavía en construcción y no está consolidada en la ESF. Conclusión: Es necesario el desarrollo de políticas de formación de profesionales sanitarios más intensas que consideren la educación popular y el uso de las metodologías activas de enseñanza como método en sus formaciones. Ese estudio podrá contribuir para una reflexión sobre el tema en la práctica y así posibilitar la construcción de una nueva mirada sobre la Educación en Salud.


Oral Health , Public Health , Health Education, Dental
16.
Int J Biol Macromol ; 97: 76-84, 2017 Apr.
Article En | MEDLINE | ID: mdl-28065754

Temporomandibular disorder is a common clinical condition involving pain in the temporomandibular joint (TMJ) region. This study assessed the antinociceptive effects of a polysulfated fraction from the red seaweed Gracilaria cornea (Gc-FI) on the formalin-induced TMJ hypernociception in rats and investigated the involvement of different mechanisms. Male Wistar rats were pretreated with injection (sc) of saline or Gc-FI 1h before intra- TMJ injection of formalin to evaluate the nociception. The results showed that pretreatment with Gc-FI significantly reduced formalin-induced nociceptive behavior. Moreover, the antinociceptive effect of the Gc-FI was blocked by naloxone (a non-selective opioid antagonist), suggesting the involvement of opioids selective receptors. Thus, the pretreatment with selective opioids receptors antagonists, reversed the antinociceptive effect of the Gc-FI in the TMJ. The Gc-FI antinociceptive effect depends on the nitric oxide/cyclic GMP/protein kinase G/ATP-sensitive potassium channel (NO/cGMP/PKG/K+ATP) pathway because it was prevented by pretreatment with inhibitors of nitric oxide synthase, guanylate cyclase enzyme, PKG and a K+ATP blocker. In addition, after inhibition with a specific heme oxygenase-1 (HO-1) inhibitor, the antinociceptive effect of the Gc-FI was not observed. Collectively, these data suggest that the antinociceptive effect induced by Gc-FI is mediated by µ/δ/κ-opioid receptors and by activation NO/cGMP/PKG/K+ATP channel pathway, besides of HO-1.


Gracilaria/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Seaweed/chemistry , Sulfates/chemistry , Temporomandibular Joint/drug effects , Analgesics/chemistry , Analgesics/isolation & purification , Analgesics/pharmacology , Animals , Cyclic GMP/metabolism , Cyclic GMP-Dependent Protein Kinases/metabolism , Formaldehyde/pharmacology , Heme Oxygenase-1/metabolism , Interleukin-10/metabolism , KATP Channels/metabolism , Male , Nociception/drug effects , Plant Extracts/isolation & purification , Rats , Rats, Wistar , Receptors, Opioid/metabolism , Serotonin/pharmacology , Signal Transduction/drug effects , Temporomandibular Joint/cytology , Temporomandibular Joint/metabolism , Trigeminal Ganglion/drug effects , Trigeminal Ganglion/metabolism
17.
Int Immunopharmacol ; 44: 160-167, 2017 Mar.
Article En | MEDLINE | ID: mdl-28107753

This study aimed to investigate the effect of sulfated polysaccharide from red seaweed Solieria filiformis (Fraction F II) in the inflammatory hypernociception in the temporomandibular joint (TMJ) of rats. Male Wistar rats were pretreated (30min) with a subcutaneous injection (s.c.) of vehicle or FII (0.03, 0.3 or 3.0mg/kg) followed by intra-TMJ injection of 1.5% Formalin or 5-hydroxytryptamine (5-HT, 225µg/TMJ). In other set of experiments rats were pretreated (15min) with an intrathecal injection of the non-selective opioid receptors Naloxone, or µ-opioid receptor antagonist CTOP, or δ-opioid receptor Naltridole hydrochloride, or κ-opioid receptor antagonist Nor-Binaltorphimine (Nor-BNI) followed by injection of FII (s.c.). After 30min, the animals were treated with an intra-TMJ injection of 1.5% formalin. After TMJ treatment, behavioral nociception response was evaluated for a 45-min observation period, animals were terminally anesthetized and periarticular tissue, trigeminal ganglion and subnucleus caudalis (SC) were collected plasma extravasation and ELISA analysis. Pretreatment with F II significantly reduced formalin- and serotonin-induced TMJ nociception, inhibit the plasma extravasation and inflammatory cytokines release induced by 1.5% formalin in the TMJ. Pretreatment with intrathecal injection of Naloxone, CTOP, Naltridole or Nor-BNI blocked the antinociceptive effect of F II in the 1.5% formalin-induced TMJ nociception. In addition, F II was able to significantly increase the ß-endorphin release in the subnucleus caudalis. The results suggest that F II has a potential antinociceptive and anti-inflammatory effect in the TMJ mediated by activation of opioid receptors in the subnucleus caudalis and inhibition of the release of inflammatory mediators in the periarticular tissue.


Analgesics, Opioid/administration & dosage , Analgesics/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Caudate Nucleus/drug effects , Pain/drug therapy , Polysaccharides/therapeutic use , Temporomandibular Joint/drug effects , Analgesics, Opioid/adverse effects , Animals , Caudate Nucleus/metabolism , Drug Interactions , Interleukin-1beta/metabolism , Male , Pain/chemically induced , Polysaccharides/chemistry , Rats , Rats, Wistar , Receptors, Opioid/metabolism , Seaweed/immunology , Sulfates/chemistry , Temporomandibular Joint/pathology , Tumor Necrosis Factor-alpha/metabolism , beta-Endorphin/metabolism
18.
Int J Biol Macromol ; 95: 1072-1081, 2017 Feb.
Article En | MEDLINE | ID: mdl-27984144

Lectins are proteins able to interact specifically and reversibly with carbohydrates. They are present in all living beings, particularly in legume seeds, which have many biological functions. The aim of this study was to isolate, characterize and verify antioxidant, anti-hemolytic, antitumor and gastroprotective activities in a lectin present in seeds of Phaseolus lunatus L. var. cascavel (PLUN). The isolation of lectin was performed by size exclusion chromatography on Sephadex G-100, which was isolated from a protein capable of agglutinating only human erythrocytes type A, being this the only inhibited haemagglutination n-acetyl-d-galactosamine. Its weight was estimated by PAGE is 128kDa. The lectin is thermostable up to 80°C and is active between pH 2-11. As 8M urea was able to denature the lectin. PLUN is a glycoprotein consisting of 2% carbohydrate and has antioxidant action with ascorbic acid equivalent antioxidant capacity (µMAA/g) of 418.20, 326 and 82.9 for total antioxidant activity, ABTS radical capture and capture of DPPH radical, respectively. The lectin has antitumor activity against melanoma derived cells at doses of 100 and 50mg/ml, reducing up to 83% tumor cells, and gastroprotective action, reducing up to 63% damaged area of ​​the stomach induced by ethanol.


Antineoplastic Agents, Phytogenic/pharmacology , Antioxidants/pharmacology , Gastrointestinal Agents/pharmacology , Phaseolus/chemistry , Plant Lectins/pharmacology , Stomach Ulcer/drug therapy , Acetylgalactosamine/chemistry , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antioxidants/chemistry , Antioxidants/isolation & purification , Benzothiazoles/antagonists & inhibitors , Benzothiazoles/chemistry , Biphenyl Compounds/antagonists & inhibitors , Biphenyl Compounds/chemistry , Cell Line, Tumor , Erythrocytes/drug effects , Ethanol , Gastrointestinal Agents/chemistry , Gastrointestinal Agents/isolation & purification , Hemagglutination Tests , Humans , Male , Mice , Molecular Weight , Picrates/antagonists & inhibitors , Picrates/chemistry , Plant Lectins/chemistry , Plant Lectins/isolation & purification , Protein Denaturation , Seeds/chemistry , Solid Phase Extraction/methods , Stomach/drug effects , Stomach/pathology , Stomach Ulcer/chemically induced , Stomach Ulcer/pathology , Sulfonic Acids/antagonists & inhibitors , Sulfonic Acids/chemistry , Urea/chemistry
19.
Basic Clin Pharmacol Toxicol ; 120(6): 523-531, 2017 Jun.
Article En | MEDLINE | ID: mdl-27883274

Parkinson's disease (PD) is characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra. The neuronal degeneration may result from the convergence of a number of different pathogenic factors, including apoptosis, excitotoxicity and oxidative stress. Many studies emphasize the importance of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in vital processes such as maintenance of the properties of cell membranes and the participation in signal transduction and biodynamic activity of neuronal membranes. In this study, the protective effect of ω-3 PUFA administration on the 6-hydroxydopamine (6-OHDA) model of PD in rats was investigated. ω-3 PUFA (1.5 and 3.0 g/kg) was orally administered by gavage during 28 consecutive days to male Wistar rats. On the 4th day, hemiparkinsonism was induced through intrastriatal injection of 6-OHDA. On the 25th day, the animals were submitted to behavioural analysis. On the 28th day, after euthanasia, the brain areas were collected for neurochemical evaluation. ω-3 PUFAs (1.5 and 3.0 g/kg) restored monoamine and amino acid levels on the striatum from hemiparkinsonian rats, followed by reduction in the number of apomorphine-induced rotations and promotion of a partial locomotor recovery. In addition, ω-3 PUFAs (1.5 and 3.0 g/kg) decreased the lipid peroxidation levels and nitrite levels in the brain areas from hemiparkinsonian rats. Thus, this study suggests that supplementation with ω-3 PUFAs prevents behavioural and neurochemical disturbances induced by 6-OHDA, presenting a potential neuroprotective action.


Dietary Supplements , Fatty Acids, Omega-3/administration & dosage , Parkinson Disease/prevention & control , Animals , Apomorphine/pharmacology , Biogenic Monoamines/analysis , Brain/drug effects , Brain/metabolism , Disease Models, Animal , Lipid Peroxidation/drug effects , Male , Motor Activity/drug effects , Nitrites/analysis , Oxidopamine , Parkinson Disease/metabolism , Rats , Rats, Wistar , gamma-Aminobutyric Acid/analysis
20.
J Oral Maxillofac Res ; 7(2): e2, 2016.
Article En | MEDLINE | ID: mdl-27489606

OBJECTIVES: The article aims to discuss the IL-1ß and TNF-α potential use as salivary biomarkers of periodontal diseases pathogenesis and progression. MATERIAL AND METHODS: This literature review has been registered in PROSPERO database with following number: CRD42016035729. Data investigation was performed on PubMed database as the main source of studies. The following search terms were used: "salivary biomarkers", "periodontal diseases", "TNF-alpha", "Interleukin-1 beta". Clinical trials and animal experimental models of periodontal disease were included in the discussion. In regards to inclusive dates, published studies from January 2006 to December 2015 were considered in this review along with the mentioned inclusion criteria. RESULTS: IL-1ß and TNF-α salivary levels increased in diseased groups, they were associated with onset and disease severity, and their levels reduced in response to periodontal therapy. IL-1ß and TNF-α could be promising biomarkers in the detection of periodontal diseases. CONCLUSIONS: The use of a salivary cytokine-based diagnosis appears to be a screening method capable of diagnosing periodontal diseases in an early fashion, establishing an era of individualized clinical decisions.

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