Explore the vast range of titles available.

The anti-inflammatory mechanisms of the sulfated polysaccharidic fraction obtained from red marine alga Gracilaria cornea (Gc-FI) were investigated using a paw edema model induced in rats by different inflammatory agents (carrageenan, dextran, serotonin, bradykinin, compound 48/80 or L-arginine). Gc-FI at the doses of 3, 9 or 27 mg/kg, subcutaneously--s.c., significantly inhibited rat paw edema induced by carrageenan and dextran, as confirmed by myeloperoxidase and Evans' blue assessments, respectively. Gc-FI (9 mg/kg, s.c.) inhibited rat paw edema induced by histamine, compound 48/80 and L-arginine. Additionally, Gc-FI (9 mg/kg, s.c.) inhibited Cg-induced edema in animals with intact mast cells but did not inhibit that with degranulated mast cells by compound 48/80, revealing a protective role on mast cell membranes. Gc-FI down-regulated the IL-1β, TNF-α and COX-2 mRNA and protein levels compared with those of the carrageenan group, based on qRT-PCR and immunohistochemistry analyses. After inhibition with ZnPP IX, a specific heme oxygenase-1 (HO-1) inhibitor, the anti-inflammatory effect of Gc-FI was not observed in Cg-induced paw edema, suggesting that the anti-inflammatory effect of Gc-FI is, in part, dependent on the integrity of the HO-1 pathway. Gc-FI can target a combination of multiple points involved in inflammatory phenomena.

To investigate de effect of PAb gel on the bone tissue of rats submitted to Bisphosphonate-related osteonecrosis of the jaws (BRONJ). Initially, 54 animals were submitted to BRONJ model by Zoledronic Acid (ZA) (0.1 mg/kg 3x/wk for 9 wk, ip), followed by the 1st upper left molar extraction at the 8th wk. After tooth removal, the animals were divided into 3 groups, ZA that received placebo gel or PAb gel that received 1% PAb gel, inside the dental alveolus. The control Group (CONTROL) received 0.1 mg/kg of 0.9% saline and then placebo gel. Three weeks after tooth extraction, the animals were euthanized, and maxillae were colleted for macroscopic, radiographic, histological and Raman spectomery assays. Additionally, GSK3b, beta-catenin, and Runx2 mRNA expressions were determined. Blood samples were collected for the analysis of Bone-specific alkaline phosphatase (BALP) levels. PAb gel improved mucosal healing, increased the number of viable osteocytes, while it reduced the number of empty lacunae, as well as the amount of bone sequestration. Furthermore, PAb gel positively influenced the number and functionality of osteoblasts by stimulating Wnt signaling, thereby inducing bone remodeling. Additionally, PAb gel contributed to improved bone quality, as evidenced by an increase in bone mineral content, a decrease in bone solubility, and an enhancement in the quality of collagen, particularly type I collagen. PAb gel mitigated bone necrosis by stimulating of bone remodeling through Wnt signaling and concurrently improved bone quality. PAb gel emerges as a promising pharmacological tool for aiding in BRONJ therapy or potentially preventing the development of BRONJ.

ObjetiveThis study aimed to evaluate the anti-resorptive activity of a semi-synthetic coumarin derivative from Platymisciumfloribundum, named 6,7-dimethoxy-3-nitrocoumarin.Material and methodsMolecular docking studies were performed to test the binding performance of the derivative against targets associated with alveolar bone loss (TNF-α, IL-1β, and catalase) and a target considered an antioxidant defense (HO-1) during periodontitis. Periodontitis was induced by placing a nylon ligature around the second molars. The rats received for 11 days 6,7-dimethoxy-3-nitrocoumarin (0.01, 0.1, or 1 mg/kg) or vehicle. We investigated by RT-qPCR analysis (TNF-α, IL-1β, and HO-1 mRNA expression levels) and by colorimetric assay (catalase activity) the mechanism of action mediated by 6,7-dimethoxy-3-nitrocoumarin. The in vivo toxicity of 6,7-dimethoxy-3-nitrocoumarin was evaluated.Results6,7-Dimethoxy-3-nitrocoumarin (0.1 or 1 mg/kg) reduced alveolar bone loss (1.05 ± 0.24), when compared to vehicle-treated group (3.05 ± 0.30). The interactions of 6,7-dimethoxy-3-nitrocoumarin and the four targets (TNF-α, IL-1β, catalase, and HO-1) showed firm bonds above 6.0 kcal/mol. 6,7-dimethoxy-3-nitrocoumarin (1 mg/kg) lowered mRNA expression levels of TNF-α (2.33 ± 0.56) and IL-1β (19.87 ± 2.9), while it increased both the mRNA expression levels of HO-1 (43.40 ± 1.05) and the catalase activity (46.42 ± 4.59), when compared to vehicle-treated group (46.29 ± 8.43; 37.83 ± 4.38; 1.58 ± 0.11; 8.93 ± 1.86, respectively). The animals did not show any signs of toxicity.Conclusion6,7-Dimethoxy-3-nitrocoumarin decreased inflammatory bone loss in the ligature-induced periodontitis in rats, and the activation of the HO-1 pathway may contribute, at least partially, to its protective effects by reducing TNF-α and IL-1β mRNA levels and increasing catalase activity.Clinical relevance6,7-Dimethoxy-3-nitrocumarin could be used as an adjunct to subgingival instrumentation during active and supportive periodontal treatment.

Periodontitis is an immuno-inflammatory disease, which can lead to tooth loss. This study aimed to investigate the efficacy of Platymiscium floribundum Vog., a Brazilian tree which has been used in folk medicine as an anti-inflammatory agent, in a pre-clinical trial of periodontitis in rats. Periodontitis was induced by placing a sterilized nylon (3.0) thread ligature around the cervix of the second left upper molar of the rats, which received (per os) P. floribundum extract (0.1, 1 or 10 mg/kg) or vehicle 1h before periodontitis-challenge and once daily during 11 days. Treatment with P. floribundum (10mg/kg) decreased alveolar bone loss, MPO activity nitrite/nitrate levels, oxidative stress, TNF-α, IL1-β, IL-8/CINC-1, and PGE2 gingival levels, and transcription of TNF-α, IL1-β, COX-2, iNOS, RANK, and RANKL genes, while elevated both BALP serum levels and IL-10 gingival levels. The animals did not show signs of toxicity throughout the experimental course. These findings show that P. floribundum has anti-inflammatory and anti-resorptive properties in a pre-clinical trial of periodontitis, representing an interesting biotechnological tool.

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-1β 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-1β 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.

Objective Marine algae are abundant sources of sulfated polysaccharides with various biological activities. Consequently, their biomolecules are of great of commercial interest. In this study, we investigated the potential antinociceptive activity of a sulfated polysaccharide obtained from the green seaweed Caulerpa racemosa (CrII) and the involvement of the hemoxigenase-1 (HO-1) pathway in its anti-inflammatory effect. Methods We used a systemic evaluation to verify possible toxic effects of Crll after consecutive treatments. Swiss mice and Wistar rats were used for all experiments. Results In Swiss mice, CrII (0.01, 0.1 and 1.0 mg/kg) significantly reduced the number of abdominal contortions and the duration of paw licking in the second phase after treatment with acetic acid and formalin, respectively. However, CrII was unable to prolong the reaction time of thermally stimulated animals. The anti-inflammatory effect of CrII (0.01, 0.1 and 1.0 mg/kg) was evidenced by a decreased number of leukocytes in the peritoneal cavities of the rats. CrII (0.01, 0.1 and 1.0 mg/kg) also reduced the amount of paw edema induced by carrageenan (Cg) and dextran. The anti-inflammatory effect of CrII was confirmed by reduced levels of myeloperoxidase in the paw tissue of the Cg groups. After inhibition with ZnPP IX, a specific HO-1 phenotype inhibitor, the anti-inflammatory effect of CrII was no longer observed in Cg-induced paw edema tests. Consecutive Crll (1.0 mg/kg) for 14 days did not change any biochemical or histopathological parameters, or cause mortality of mice. Conclusions CrII did not produce any signs of toxicity and effectively decreased nociception and inflammation. Also, the anti-inflammatory effect of Crll is at least in part dependent on the integrity of the HO-1 pathway.

Egletes viscosa (L.) Less., Asteraceae (with the vernacular name of “macela”), is known for its gastroprotective properties in traditional medicine in Brazil. Herein, we evaluated the toxicity and antiresorptive activity of 12-acetoxyhawtriwaic acid lactone, a diterpene obtained from E. viscosa . 12-Acetoxyhawtriwaic acid lactone has been demonstrated to have biological effects which might be important during periodontitis, a bone disorder. Molecular docking studies analyzed ADME-Tox properties of 12-acetoxyhawtriwaic acid lactone and evaluated its binding performance against targets associated with bone loss. Periodontitis was induced by a ligature around the mandibular first molars. The mice received (gavage) 12-acetoxyhawtriwaic acid lactone (12.5, 25, 50 mg/kg) for 14 days. Bone loss was assessed through morphometric and histometric analysis. Picrosirius Red staining was performed in mandible sections. We investigated in gingival tissues by RT-qPCR RANK-L/OPG and catalase mRNA expression levels, and by colorimetric assay catalase and superoxide dismutase activities. The in vivo toxicity of 12-acetoxyhawtriwaic acid lactone was evaluated. In silico assays suggested good oral bioavailability and hepatotoxicity, and the interactions of 12-acetoxyhawtriwaic acid lactone with RANKL/OPG and catalase showed firm bonds. In in vivo experiments, 12-acetoxyhawtriwaic acid lactone reduced bone loss. Although 12-acetoxyhawtriwaic acid lactone (25 or 50 mg/kg) produced liver and renal toxicity, it (12.5 mg/kg) showed no signs of toxicity, increased collagen type I, reduced RANK-L mRNA levels and increased OPG and catalase mRNA levels, and enhanced catalase and superoxide dismutase activities. 12-Acetoxyhawtriwaic acid lactone (12.5 mg/kg) was safe and had anti-resorptive effects during periodontitis in mice, showing antioxidant activity with the involvement of the RANK-L/OPG pathway. These findings point to a novel application for E. viscosa and highlights the need for cautious utilization of medicinal plants. Graphical Abstract

Aims. To establish a new model of zymosan-induced temporomandibular joint (TMJ) arthritis in the rat and to investigate the role of nitric oxide. Methods. Inflammation was induced by an intra-articular injection of zymosan into the left TMJ. Mechanical hypernociception, cell influx, vascular permeability, myeloperoxidase activity, nitrite levels, and histological changes were measured in TMJ lavages or tissues at selected time points. These parameters were also evaluated after treatment with the nitric oxide synthase (NOS) inhibitors L-NAME or 1400 W. Results. Zymosan-induced TMJ arthritis caused a time-dependent leucocyte migration, plasma extravasation, mechanical hypernociception, and neutrophil accumulation between 4 and 24 h. TMJ immunohistochemical analyses showed increased inducible NOS expression. Treatment with L-NAME or 1400 W inhibited these parameters. Conclusion. Zymosan-induced TMJ arthritis is a reproducible model that may be used to assess both the mechanisms underlying TMJ inflammation and the potential tools for therapies. Nitric oxide may participate in the inflammatory temporomandibular dysfunction mechanisms.

Objective Wide biotechnological investigations of only a limited number of seaweed lectins have been performed. We previously demonstrated the anti-nociceptive and anti-inflammatory effects of a lectin isolated from the green seaweed Caulerpa cupressoides var. lycopodium (CcL). Herein, we further studied the mechanisms of action of CcL. Methods Classical acute inflammation models induced by different flogistic agents were used to evaluate the anti-inflammatory action of CcL. CcL was injected locally into the rat paw to verify a possible pro-inflammatory outcome. Results CcL (0.1, 1 or 10 mg/kg; i.v.) reduced the carrageenan-induced rat paw edema and neutrophilic infiltration, which was not altered by either mucin (inhibitor of CcL carbohydrate-binding site) or ZnPP-IX (specific HO-1 inhibitor). Immunohistochemical analyses showed that CcL (1 mg/kg) reduced the expression of the cytokines IL-1β, TNF-α, IL-6 and COX-2. CcL (0.1, 1 or 10 mg/kg) inhibited dextran, and CcL (1 mg/kg) inhibited histamine-induced rat paw edema. Both effects were reversed by mucin inhibition. CcL (1 mg/kg) was ineffective for the treatment of serotonin- and bradykinin-induced rat paw edema. When injected via the i.pl. route, CcL (10 mg/kg) elicited rat paw edema involving a wide range of mediators. Conclusions The anti-inflammatory action of CcL involves the inhibition of IL-1β, TNF-α, IL-6 and COX-2 expression and histamine H 1 receptors. When locally administered, CcL exerts pro-inflammatory actions.

The purpose of this study was to review the effects of nonsteroidal anti-inflammatory drugs on osseointegration and determine whether they cause failures in dental implants and whether patients who use them chronically can receive dental implants safely. A bibliographic electronic search was performed using the Cochrane Library, PubMed, and Medline databases, selecting articles published between January 1982 and December 2012. The search included the following keywords, either alone or combined: “nonsteroidal anti-inflammatory drugs,” “dental implants,” “bone healing,” and “osteoprogenitor cells.” The inclusion criteria were the following: randomized, double-blind, placebo-controlled clinical studies, in vivo animal model studies of osseointegration, and in vitro studies of the effects of these agents on osteoprogenitor cells. The literature search revealed 360 references. A total of 31 articles met the inclusion criteria, including 2 clinical trials, 20 animal studies, and 9 osteoprogenitor cell studies. The clinical trials revealed that cyclooxygenase-1 (COX-1) inhibitors did not impair osseointegration. The animal studies showed that any drug that is capable of inhibiting COX-2 may impair the osseointegration process. The in vitro studies showed that COX-2 inhibitors are the most potent depressors of osseointegration at the cellular level. Caution must be taken when selecting COX-2 nonsteroidal anti-inflammatory drugs during the postoperative period.