Intestinal mucositis, characterized by inflammatory and/or ulcerative processes in the gastrointestinal tract, occurs due to cellular and tissue damage following treatment with 5-fluorouracil (5-FU). ...Rutin (RUT), a natural flavonoid extracted from
, exhibits antioxidant, anti-inflammatory, cytoprotective, and gastroprotective properties. However, the effect of RUT on inflammatory processes in the intestine, especially on mucositis promoted by antineoplastic agents, has not yet been reported. In this study, we investigated the role of RUT on 5-FU-induced experimental intestinal mucositis. Swiss mice were randomly divided into seven groups: Saline, 5-FU, RUT-50, RUT-100, RUT-200, Celecoxib (CLX), and CLX + RUT-200 groups. The mice were weighed daily. After treatment, the animals were euthanized and segments of the small intestine were collected to evaluate histopathological alterations (morphometric analysis); malondialdehyde (MDA), myeloperoxidase (MPO), and glutathione (GSH) concentrations; mast and goblet cell counts; and cyclooxygenase-2 (COX-2) activity, as well as to perform immunohistochemical analyses. RUT treatment (200 mg/kg) prevented 5-FU-induced histopathological changes and reduced oxidative stress by decreasing MDA concentrations and increasing GSH concentrations. RUT attenuated the inflammatory response by decreasing MPO activity, intestinal mastocytosis, and COX-2 expression. These results suggest that the COX-2 pathway is one of the underlying protective mechanisms of RUT against 5-FU-induced intestinal mucositis.
Intestinal mucositis is a common complication associated with 5-fluorouracil (5-FU), a chemotherapeutic agent used for cancer treatment. Troxerutin (TRX), a semi-synthetic flavonoid extracted from
, ...has been reported as a potent antioxidant and anti-inflammatory agent. In the present study, we aimed to evaluate the effect of TRX on 5-FU-induced intestinal mucositis. Swiss mice were randomly divided into seven groups: Saline, 5-FU, TRX-50, TRX-100, TRX-150, Celecoxib (CLX), and CLX + TRX-100. The weight of mice was measured daily. After treatment, the animals were euthanized and segments of the small intestine were collected to evaluate histopathological alterations (morphometric analysis), levels of malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH), mast and goblet cell counts, immunohistochemical analysis, and cyclooxygenase-2 (COX-2) activity. Compared to the saline treatment, the 5-FU treatment induced intense weight loss and reduction in villus height. TRX treatment (100 mg/kg) prevented the 5-FU-induced histopathological changes and decreased oxidative stress by decreasing the MDA levels and increasing GSH concentration. TRX attenuated inflammatory process by decreasing MPO activity, intestinal mastocytosis, and COX-2 expression. TRX also reversed the depletion of goblet cells. Our findings suggest that TRX at a concentration of 100 mg/kg had chemopreventive effects on 5-FU-induced intestinal mucositis via COX-2 pathway.
We examined the effects of treatment with 1-nitro-2-phenylethane (NP), a novel soluble guanylate cyclase stimulator, on monocrotaline (MCT)-induced PAH in rats.
At day 0, male adult rats were ...injected with a single subcutaneous (s.c.) dose of monocrotaline (60 mg/kg). Control (CNT) rats received an equal volume of monocrotaline's vehicle only (s.c.). Four weeks later, MCT-treated rats were treated orally for 14 days with NP (50 mg/kg/day) (MCT-NP group) or its vehicle (Tween 2%) (MCT-V group). At the end of the treatment period and before invasive hemodynamic study, rats of all experimental groups were examined by echocardiography.
With respect to CNT rats, MCT-V rats showed significant; (1) increases in pulmonary artery (PA) diameter, RV free wall thickness and end-diastolic RV area, and increase of Fulton index; (2) decreases in maximum pulmonary flow velocity, PA acceleration time (PAAT), PAAT/time of ejection ratio, and velocity-time integral; (3) increases in estimated mean pulmonary arterial pressure; (4) reduction of maximal relaxation to acetylcholine in aortic rings, and (5) increases in wall thickness of pulmonary arterioles. All these measured parameters were significantly reduced or even abolished by oral treatment with NP.
NP reversed endothelial dysfunction and pulmonary vascular remodeling, which in turn reduced ventricular hypertrophy. NP reduced pulmonary artery stiffness, normalized the pulmonary artery diameter and alleviated RV enlargement. Thus, NP may represent a new therapeutic or a complementary approach to treatment of PAH.
Rheumatoid arthritis (RA) is a systemic and progressive inflammatory disease characterized by synovial inflammation and hyperplasia, production of autoantibodies and destruction of cartilage and ...bone. The etiology of RA has yet to be elucidated and numerous joints have shown limited functions. It is estimated that 65% of patients with this disease have symptoms in the temporomandibular joint (TMJ), but the nociceptive, histopathological and immunological alterations of RA in this joint are poorly reported. Experimental models are essential in order to better understand the pathological mechanisms underlying the tissue breakdown and the development of new therapeutic approaches. Actually, the experimental model of RA in TMJ is induced by one injection of methylated bovine serum albumin (mBSA) to reproduced acute phase of RA. Thus, the aim of this study was to update an experimental model of chronic RA with booster injections of mBSA and evalute the morphological alterations in TMJ. 24 male Wistar rats (180 – 220g), originating from the Central Animal Facility of the Federal University of Ceará – Brazil, kept at 22°C, by day/night cicle – 12/12 h, with water and food ad libitum. Initially, the animals were sensitized with an emulsion containing methylated mBSA and Complete Freund Adjuvant (CFA), subcutaneously administered. Booster injections of mBSA dissolved in Incomplete Freund Adjuvant (IFA) were administered 7 and 14 days after the first immunization. 21 days after initial injections, arthritis in the left TMJ was induced in immunized animals by an intra‐articular injection of mBSA (10 μg/i.art.). Booster injections of mBSA were given on days 28 and 35. The animals were euthanized 24 h after each mBSA injection in the left TMJ. The Control group did not receive intra‐articular mBSA injections. The animals that received 1, 2 or 3 mBSA injections in the left TMJ, received saline (0,9%; 10 μl; i.art) in the right TMJ. The animals were divided in 4 groups (n=6): control, mBSA (1), mBSA (2), mBSA (3). Nociceptive threshold was performed during the whole experiment using an analgesymeter. After 24h of mBSA injections, synovial fluid was extracted for a total cell count and TMJs were removed for histopathological and immunohistochemical analysis for IL‐1β, IL‐6 and TNF‐α. The mechanical allodynia evaluation in the left TMJ showed that, during the subcutaneous administration of mBSA, there was no alteration on the nociceptive threshold in the TMJ (FIGURE 1A). But, during mBSA intra‐articular injection, a significant reduction of nociceptive threshold was observed (p =0.000) (FIGURE 1B). The saline administered in the right TMJ of rats that received 1, 2 or 3 injections of mBSA in the left TMJ showed no statistical difference compared to the control group. The mBSA (2) and mBSA (3) groups showed an intense mononuclear inflammatory infiltrate, thickening of the articular disc, but only the group that received 3 mBSA injections showed extensive joint destruction and an increase of cellular influx (FIGURE 1C AND 1D). In the immunohistochemistry, IL‐1β, IL‐6 and TNF‐α expression were increased in the synoviocytes layer, joint cartilage and synovial membrane in the groups that received 2 and 3 mBSA injections in TMJ (p <0.05) (FIGURE 2A, 2B AND 2C). In conclusion, this new experimental approach simulates the chronic RA in TMJ because shows nociceptive, histopathological and immunological clinical findings similar to human RA.
This is from the Experimental Biology 2018 Meeting. There is no full text article associated with this published in The FASEB Journal.
No campo do turismo, as políticas públicas nacionais de qualificação ganharam destaque nos últimos vinte anos. No entanto, existem dualidades na própria constituição da política de qualificação ...promovida pelo Ministério do Turismo e uma consequência da sua organização caótica é a falta de clareza dos rumos que a política aponta. Assim, o objetivo desta pesquisa é analisar a disputa política presente nos discursos sobre turismo, trabalho e educação que permeiam a política pública nacional de qualificação profissional em turismo. O percurso teórico-metodológico desta investigação possui três parâmetros: no campo epistemológico, o paradigma da complexidade; no campo metodológico, a análise do discurso; e, no campo teórico, as obras de Krippendorf, Freire e Marx. Como resultado, foram analisadas as formações discursivas do turismo (duro e suave), do trabalho (alienado e não alienado) e da educação (bancária e libertadora) e as formações ideológicas que os regem (do empresário e do ser humano). Diante dos antagonismos e complementaridades entre as duas formações ideológicas, a do empresário se impõe porque consegue incorporar as relações dialógicas e fazer com que a do ser humano atenda ao seu propósito.
Oral mucositis is an inflammation of the oral mucosa mainly resulting from the cytotoxic effect of 5-fluorouracil (5-FU). The literature shows anti-inflammatory action of
l
-cysteine (
l
-cys) ...involving hydrogen sulfide (H
2
S). In view of these properties, we investigate the effect of
l
-cys in oral mucositis induced by 5-FU in hamsters. The animals were divided into the following groups: saline 0.9%, mechanical trauma, 5-FU 60–40 mg/kg,
l
-cys 10/40 mg and NaHS 27 µg/kg. 5-FU was administered on days 1st to 2nd; 4th day excoriations were made on the mucosa; 5th–6th received
l
-cys and NaHS. For data analysis, histological analyses, mast cell count, inflammatory and antioxidants markers, and immunohistochemistry (cyclooxygenase-2(COX-2)/inducible nitric oxide synthase (iNOs)/H
2
S) were performed. Results showed that
l
-cys decreased levels of inflammatory markers, mast cells, levels of COX-2, iNOS and increased levels of antioxidants markers and H
2
S when compared to the group 5-FU (
p
< 0.005). It is suggested that
l
-cys increases the H
2
S production with anti-inflammatory action in the 5-FU lesion.
Zoledronic acid (ZA) is often prescribed for osteoporosis or resorptive metabolic bone disease. This study aims to evaluate the effect of ZA on orthodontic tooth movement (OTM) and root and bone ...resorption and its repercussion on root, periodontal ligament and alveolar bone tissues. The experimental group consisted of 72 Wistar rats divided in four subgroups: Naive, Saline and Zoledronic Acid groups at the concentration of 0.2 mg/kg ZA (0.2) or 1.0 mg/kg ZA (1.0). The animals were subjected to i.v (dorsal penile vein) administrations of ZA or saline solution, on days 0, 7, 14 and 42. Under anesthesia, NiTi springs were installed in the first left maxillary molar with 50gf allowing the OTM, except for the negative control group (N) for mesial movement of the left first maxillary teeth. The animals were sacrificed and maxillae were removed for macroscopic and histopathological analyzes, scanning electron microscopy, computerized microtomography and confocal microscopy. Treatment with ZA decreased the OTM and the number of osteoclasts and loss of alveolar bone when compared to the naive and saline groups. Reduction of radicular resorption, increased necrotic areas and reduced vascularization in the periodontal ligament were observed in the ZA groups. ZA interferes with OTM and presents anti-resorptive effects on bone and dental tissues associated with a decreased vascularization, without osteonecrosis.
Dietary supplementation with pterostilbene (PS) and/or a probiotic (PRO) may ameliorate the intestinal microbiota in disease conditions. This study aims to evaluate PS and PRO for the chemoprevention ...of putative precursor lesions for colorectal cancer (CRC) in an experimental model of intestinal carcinogenesis with 1,2-dimethylhydrazine (1,2-DMH). Sixty male Wistar rats were equally divided into five groups: Sham, 1,2-DMH, 1,2-DMH + PS, 1,2-DMH + PRO, and 1,2-DMH + PS + PRO. PRO (5 × 10
/mL) was offered in water, and PS (300 ppm) was provided in the diet ad libitum. 1,2-DMH (20 mg/kg/week) was administered for 15 consecutive weeks. In the 25th week, proctocolectomy was conducted. PRO alone and PRO combined with PS were the best intervention strategies to improve experimental 1,2-DMH-induced CRC regarding several parameters of carcinogenesis. Our findings may contribute to the development of novel preventive strategies for CRC and may help to identify novel modulators of colon carcinogenesis.
Acute kidney injury (AKI) remains a great problem in clinical practice. Renal ischemia/reperfusion (I/R) injury is a complex pathophysiological process. Propolis is a natural polyphenol-rich resinous ...substance collected by honeybees from a variety of plant sources that has anti-inflammatory and anti-oxidative properties. Red propolis (RP) protection in renal I/R injury was investigated.
Male Wistar rats underwent unilateral nephrectomy and contralateral renal I/R (60 min). Rats were divided into four groups: (1) sham group, (2) RP group (sham-operated rats treated with RP), 3) IR group (rats submitted to ischemia) and (4) IR-RP (rats treated with RP before ischemia). At 48 h after reperfusion, renal function was assessed and kidneys were removed for analysis.
I/R increased plasma levels of creatinine and reduced creatinine clearance (CrCl), and RP provided protection against this renal injury. Red propolis significantly improves oxidative stress parameters when compared with the IR group. Semiquantitative assessment of the histological lesions showed marked structural damage in I/R rats compared with the IR-RP rats. RP attenuates I/R-induced endothelial nitric oxide-synthase down regulation and increased heme-oxygenase expression in renal tissue.
Red propolis protects kidney against acute ischemic renal failure and this protection is associated with reduced oxidative stress and eNOS and heme-oxygenase up regulation.
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