Epiisopiloturine (EPI) is an important imidazole alkaloid because of its pharmacological properties. The aim of this study was to investigate the effects of epiisopiloturine on inflammatory ...parameters of the colonic mucosa in a rat model of Crohn’s disease (CD). For this, we induced colitis using trinitrobenzenosulfonic acid and determined myeloperoxidase (MPO), interleukin 1 β (IL-1β), glutathione (GSH), and malondialdehyde (MDA) levels in the intestinal mucosa. The location and expression of the inflammatory markers in the colon were investigated by immunohistochemistry for NO synthase induced (iNOS), interleukin 1 beta (IL-1β), and cyclooxygenase-2 (COX-2) and western blotting (iNOS and COX-2), respectively. Compared with TNBS alone, epiisopiloturine at 1 mg/kg reduced the macroscopic and microscopic scores, wet weight of the colon, and neutrophilic infiltration and expression of the pro-inflammatory cytokine IL-1β. Epiisopiloturine at 1 mg/kg maintained or restored GSH levels and simultaneously decreased MDA levels. Animals treated with epiisopiloturine exhibited reduced immunostaining for IL-1β, iNOS, and COX-2 and reduced cell count per field. Epiisopiloturine reduced the expression of COX-2 and iNOS in the colon. Based on these findings, we conclude that epiisopiloturine at 1 mg/kg may be an important pharmacological tool against intestinal inflammatory diseases due to its inhibitory action on key enzymes and products involved in inflammation.
Highlights • The fatty acid mixture tested in this study (high ω-9:ω-6 ratio and low ω-6:ω-3 ratio) effectively reduced TNF-α levels post tooth extraction in rats. • The fatty acid mixture tested in ...this study (high ω-9:ω-6 ratio and low ω-6:ω-3 ratio) effectively reduced myeloperoxidase levels post tooth extraction in rats. • Clinically the fatty acid mixture tested in this study (high ω-9:ω-6 ratio and low ω-6:ω-3 ratio) effectively reduced masseter edema post tooth extraction in rats. • Histologically the fatty acid mixture tested in this study (high ω-9:ω-6 ratio and low ω-6:ω-3 ratio) effectively reduced osteoclast numbers at the site of dental extraction in rats.
The canonical Wnt pathway participates in inflammatory diseases and it is involved in neuropathic pain. This study evaluated the immunoexpression of the canonical Wnt signaling pathway in the ...articular cartilage of the temporomandibular joint (TMJ) and along the nociceptive trigeminal pathway in arthritic rats. For this, male Wistar rats were divided into Control (C) and Arthritic (RA) groups. Arthritis induction was performed through subcutaneous injection of methylated bovine serum albumin (mBSA) and complete Freund Adjuvant (CFA)/ Incomplete Freund Adjuvant (IFA) on the first 14 days (once a week), followed by 3 weekly intra-articular injections of mBSA (10 μl/joint; left TMJ). The following parameters were evaluated: nociceptive threshold, inflammatory infiltrate, type I and III collagen birefringence, immunohistochemistry for IL-1β, TNF-α, IL-6, Wnt10b, β-catenin, cyclin-D1 in articular cartilage, c-Myc in synovial membrane, and immunofluorescence analysis for c-Fos, Wnt-10b and β-catenin in the trigeminal ganglion and the trigeminal subnucleus caudalis. The RA group showed intense articular cartilage damage with proliferation of type III collagen, increased immunoexpression of proinflammatory cytokines and Wnt-10b, β-catenin and cyclin-D1 in the articular cartilage and c-Myc in the synovial membrane. In the RA group, a reduction in the nociceptive threshold was observed, followed by a significant increase in the expression of Wnt-10b in neurons and β-catenin in satellite cells of the trigeminal ganglion. c-Fos immunoexpression was observed in neurons, peripherally and centrally, in arthritic rats. Our data demonstrated that TMJ arthritis in rats causes articular cartilage damage and nociceptive behavior, with increased immunoexpression of canonical Wnt pathway in the articular cartilage and trigeminal ganglion.
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•TMJ arthritis in rats causes mechanical hyperalgesia and increased inflammatory parameters.•Canonical Wnt markers are increased in the TMJ of the arthritic rats.•This signaling pathway contributes to the TMJ articular cartilage damage in this experimental model.•Wnt/β-catenin signaling pathway can be involved in the peripheral painful sensitization in the TMJ arthritis in rats
The soluble guanylate cyclase (sGC)/GMPc pathway plays an important role in controlling pulmonary arterial hypertension (PAH). We investigated whether the novel sGC stimulator ...trans-4-methoxy-β-nitrostyrene (T4MN), ameliorates monocrotaline (MCT)-induced PAH. At Day 0, rats were injected with MCT (60 mg/kg, s. c.). Control (CNT) rats received an equal volume of monocrotaline vehicle only (s.c.). Four weeks later, MCT-treated rats were orally treated for 14 days with T4MN (75 mg/kg/day) (MCT-T4MN group) or its vehicle (MCT-V group), and with sildenafil (SIL; 50 mg/kg) (MCT-SIL group). Compared to the CNT group, MCT treatment induced a significant increase in both the Fulton index and RV systolic pressure but significantly reduced the maximum relaxation induced by acetylcholine. Indeed, MCT treatment increased the wall thickness of small and larger pulmonary arterioles. Oral treatment with T4MN and SIL reduced the Fulton index and RV systolic pressure compared to the MCT-V group. Maximum relaxation induced by acetylcholine was significantly enhanced in MCT-SIL group. Both T4MN and SIL significantly reduced the enhanced wall thickness of small and larger pulmonary arterioles. Treatment with T4MN has a beneficial effect on PAH by reducing RV systolic pressure and consequently right ventricular hypertrophy, and by reducing pulmonary artery remodeling. T4MN may represent a new therapeutic or complementary approach for the treatment of PAH.
This study investigated the anti-inflammatory activity of the extract (LEG) and purified (LPG) lycopene from guava (Psidium guajava L.), as well as some mechanisms possibly involved in this effect. ...The anti-inflammatory activity was initially assessed using paw edema induced by Carrageenan, Dextran, Compound 48/80, Histamine and Prostaglandin E2 in Swiss mice. A peritonitis model was used to evaluate neutrophil migration, the activity of myeloperoxidase (MPO) and reduced glutathione (GSH) concentration; while the effect on the expression of iNOS, COX-2 and NF-κB, was assessed by immunohistochemistry analysis. Results showed that oral and intraperitoneal administration of LEG and LPG inhibited inflammation caused by carrageenan. LPG (12.5mg/kg p.o.) significantly inhibited the edema formation induced by different phlogistic agents and immunostaining for iNOS, COX-2 and NF-κB. Leukocytes migration in paw tissue and peritoneal cavity was reduced, as well as MPO concentration, whereas GSH levels increased. Thus, lycopene-rich extract from red guava has beneficial effect on acute inflammation, offering protection against the consequences of oxidative stress by downregulating inflammatory mediators and inhibiting gene expression involved in inflammation.
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•Lycopene Extract (LEG) and purified lycopene (LPG) from red guava exhibited beneficial effect on acute inflammation.•LPG was selected for the subsequent analysis of the anti-inflammatory effect observed.•LPG acts decreasing oxidative stress and the modulation of inflammatory mediators.•LPG prevents cell recruitment and iNOS, COX-2 and NF-κB expression.
The present study aims to evaluate the gastroprotective potential of riparin III in the acute model of gastric lesions induced by ethanol in mice. Riparin III was synthesized and structurally ...characterized. Macroscopic evaluations were used through histopathologic tests, in addition to studying the mechanism of action. It also performed biochemical tests, such as nitrite/nitrate levels, reduced glutathione content and malondialdehyde determination. Furthermore, the involvement of iNOS in the gastroprotective effect was evaluated by immunohistochemistry. The results showed the gastroprotective effect of the riparin III, as demonstrated by the reduction of epithelial cell loss, edema, inflammatory infiltrate, and in the number of mast cells. It was also observed that pretreatment with
l
-NAME and glibenclamide reversed the gastroprotective effect of riparin III, which suggests the participation of ATP-sensitive potassium channels and nitric oxide in the observed effects by the substance under study. Nitrite levels were restored and there was a decreased lipid peroxidation and increased content of reduced glutathione. The immunohistochemical analysis evidenced the participation of iNOS in the gastroprotective effect of riparin III, which corroborated with the nitrite/nitrate dosage and participation of the nitric oxide pathway. Thus, riparin III presented gastroprotective activity and antioxidant potential against ethanol-induced injuries.
Graphical Abstract
to describe the nursing care performed by the nursing team to the person with mental disorder submitted to ECT and to analyze the implications of the Psychiatric Reform in this care.
socio-historical ...study, which uses the Thematic Oral History method.
the nursing team is present in a continuous way in the monitoring of people submitted to ECT, performing care before, during and after the same, as well as visualizing the evolution of the technique and also of nursing care itself, however, does not recognize the Psychiatric Reform as agent for this change.
the Brazilian Psychiatric Reform triggered a process of humanization of nursing knowledge, influencing the care of the person with mental disorder submitted to ECT, with this, care practices also changed, a law was approved, regulating its practice, and its application was decreasing.
Severe loss of bone mass may require grafting, and, among the alternatives available, there are natural biomaterials that can act as scaffolds for the cell growth necessary for tissue regeneration. ...Collagen and elastin polymers are a good alternative due to their biomimetic properties of bone tissue, and their characteristics can be improved with the addition of polysaccharides such as chitosan and bioactive compounds such as jatoba resin and pomegranate extract due to their antigenic actions. The aim of this experimental protocol was to evaluate bone neoformation in experimentally made defects in the mandible of rats using polymeric scaffolds with plant extracts added. Thirty rats were divided into group 1, with a mandibular defect filled with a clot from the lesion and no graft implant (G1-C,
= 10); group 2, filled with collagen/chitosan/jatoba resin scaffolds (G2-CCJ,
= 10); and group 3, with collagen/nanohydroxyapatite/elastin/pomegranate extract scaffolds (G3-CHER,
= 10). Six weeks after surgery, the animals were euthanized and samples from the surgical areas were submitted to macroscopic, radiological, histological, and morphometric analysis of the mandibular lesion repair process. The results showed no inflammatory infiltrates in the surgical area, indicating good acceptance of the scaffolds in the microenvironment of the host area. In the control group (G1), there was a predominance of reactive connective tissue, while in the grafted groups (G2 and G3), there was bone formation from the margins of the lesion, but it was still insufficient for total bone repair of the defect within the experimental period standardized in this study. The histomorphometric analysis showed that the mean percentage of bone volume formed in the surgical area of groups G1, G2, and G3 was 17.17 ± 2.68, 27.45 ± 1.65, and 34.07 ± 0.64 (mean ± standard deviation), respectively. It can be concluded that these scaffolds with plant extracts added can be a viable alternative for bone repair, as they are easily manipulated, have a low production cost, and stimulate the formation of new bone by osteoconduction.
ABSTRACT Purpose: To analyze the potential of tumor necrosis factor-α (TNF-α) and factor nuclear kappa B (NF-κB) as colorectal cancer (CRC) biomarkers in an experimental model of intestinal ...carcinogenesis with 1,2-dimethyhydrazine (1,2-DMH). Methods: Twenty-four male Wistar rats were divided into two groups: sham and 1,2-DMH. First, 1,2-DMH (20 mg/kg/week) was administered for 15 consecutive weeks. In the 25th week, proctocolectomy was conducted. Histopathological analysis, immunohistochemistry, and gene expression of TNF-α and NF-κB were performed. Statistical analysis was performed using GraphPad Prism. The location of aberrant crypt foci (ACF) was analyzed by Kruskal-Wallis’ test. For analyses with two groups with parametric data, the t-test was used; for non-parametric data, the Mann-Whitney’s test was used. P < 0.05 was considered significant. Results: The number of ACF and macroscopic lesions was significantly higher (p < 0.5) in the 1,2-DMH group compared to the sham group, and most ACF were concentrated in the distal segment of the colon. There was a statistically significant increase (p < 0.5) in protein and gene expression of TNF-α and NF-κB in the 1,2-DMH group compared to the sham group. Conclusions: Our results provide supportive evidence that TNF-α and NF-κB pathways are strongly involved in CRC development in rats and might be used as early biomarkers of CRC pathogenesis in experimental studies.
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