scholarly journals Troxerutin Prevents 5-Fluorouracil Induced Morphological Changes in the Intestinal Mucosa: Role of Cyclooxygenase-2 Pathway

2020 ◽  
Vol 13 (1) ◽  
pp. 10 ◽  
Author(s):  
João Antônio Leal de Miranda ◽  
Conceição da Silva Martins ◽  
Lázaro de Sousa Fideles ◽  
Maria Lucianny Lima Barbosa ◽  
João Erivan Façanha Barreto ◽  
...  
Keyword(s):  
Chemotherapeutic Agent ◽  
Morphological Changes ◽  
Immunohistochemical Analysis ◽  
Cyclooxygenase 2 ◽  
Villus Height ◽  
Inflammatory Agent ◽  
Cell Counts ◽  
Intestinal Mucositis ◽  
Cox 2

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 Dimorphandra gardneriana, 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.

scholarly journals Protective Effect of Cashew Gum (Anacardium occidentale L.) on 5-Fluorouracil-Induced Intestinal Mucositis

2019 ◽  
Vol 12 (2) ◽  
pp. 51 ◽  
Author(s):  
João Antônio Leal de Miranda ◽  
João Erivan Façanha Barreto ◽  
Dainesy Santos Martins ◽  
Paulo Vitor de Souza Pimentel ◽  
Deiziane Viana da Silva Costa ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Immunohistochemical Analysis ◽  
Saline Group ◽  
Anacardium Occidentale ◽  
Interleukin 1 Beta ◽  
Villus Height ◽  
Cashew Gum ◽  
Inflammatory Agent ◽  
Intestinal Mucositis ◽  
Cox 2

Intestinal mucositis is a common complication associated with 5-fluorouracil (5-FU), a chemotherapeutic agent used for cancer treatment. Cashew gum (CG) has been reported as a potent anti-inflammatory agent. In the present study, we aimed to evaluate the effect of CG extracted from the exudate of Anacardium occidentale L. on experimental intestinal mucositis induced by 5-FU. Swiss mice were randomly divided into seven groups: Saline, 5-FU, CG 30, CG 60, CG 90, Celecoxib (CLX), and CLX + CG 90 groups. 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), and glutathione (GSH), and immunohistochemical analysis of interleukin 1 beta (IL-1β) and cyclooxygenase-2 (COX-2). 5-FU induced intense weight loss and reduction in villus height compared to the saline group. CG 90 prevented 5-FU-induced histopathological changes and decreased oxidative stress through decrease of MDA levels and increase of GSH concentration. CG attenuated inflammatory process by decreasing MPO activity, intestinal mastocytosis, and COX-2 expression. Our findings suggest that CG at a concentration of 90 mg/kg reverses the effects of 5-FU-induced intestinal mucositis.

scholarly journals Role of Rutin in 5-Fluorouracil-Induced Intestinal Mucositis: Prevention of Histological Damage and Reduction of Inflammation and Oxidative Stress

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2786
Author(s):  
Lázaro de Sousa Fideles ◽  
João Antônio Leal de Miranda ◽  
Conceição da Silva Martins ◽  
Maria Lucianny Lima Barbosa ◽  
Helder Bindá Pimenta ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Mechanisms ◽  
Cell Counts ◽  
Histological Damage ◽  
Inflammatory Processes ◽  
Intestinal Mucositis ◽  
Cox 2 ◽  
And Oxidative Stress ◽  
Immunohistochemical Analyses

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 Dimorphandra gardneriana, 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.

Potential role of the NADPH oxidase NOX1 in the pathogenesis of 5-fluorouracil-induced intestinal mucositis in mice

2012 ◽  
Vol 302 (10) ◽  
pp. G1133-G1142 ◽  
Author(s):  
Masashi Yasuda ◽  
Shinichi Kato ◽  
Naoki Yamanaka ◽  
Maho Iimori ◽  
Daichi Utsumi ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Caspase 3 ◽  
Potential Role ◽  
Chemotherapeutic Agent ◽  
Wild Type ◽  
Villus Height ◽  
Tnf Α ◽  
Nadph Oxidase 1 ◽  
Intestinal Mucositis

Although NADPH oxidase 1 (NOX1) has been shown to be highly expressed in the gastrointestinal tract, the physiological and pathophysiological roles of this enzyme are not yet fully understood. In the present study, we investigated the role of NOX1 in the pathogenesis of intestinal mucositis induced by the cancer chemotherapeutic agent 5-fluorouracil (5-FU) in mice. Intestinal mucositis was induced in Nox1 knockout (Nox1KO) and littermate wild-type (WT) mice via single, daily administration of 5-FU for 5 days. In WT mice, 5-FU caused severe intestinal mucositis characterized by a shortening of villus height, a disruption of crypts, a loss of body weight, and diarrhea. In Nox1KO mice, however, the severity of mucositis was significantly reduced, particularly with respect to crypt disruption. The numbers of apoptotic caspase-3- and caspase-8-activated cells in the intestinal crypt increased 24 h after the first 5-FU administration but were overall significantly lower in Nox1KO than in WT mice. Furthermore, the 5-FU-mediated upregulation of TNF-α, IL-1β, and NOX1 and the production of reactive oxygen species were significantly attenuated in Nox1KO mice compared with that in WT mice. These findings suggest that NOX1 plays an important role in the pathogenesis of 5-FU-induced intestinal mucositis. NOX1-derived ROS production following administration of 5-FU may promote the apoptotic response through upregulation of inflammatory cytokines.

Immunohistochemical Expression of Cyclooxygenase 2 in Follicular Carcinomas of the Thyroid

2005 ◽  
Vol 129 (6) ◽  
pp. 736-741 ◽  
Author(s):  
Denise M. Haynik ◽  
Richard A. Prayson
Keyword(s):  
Follicular Adenoma ◽  
Immunohistochemical Analysis ◽  
Cyclooxygenase 2 ◽  
Positive Staining ◽  
Limited Data ◽  
Immunohistochemical Expression ◽  
Cox 2 ◽  
Disease Free

Abstract Context.—Cyclooxygenase 2 (COX-2) has been shown to be up-regulated and/or overexpressed in a variety of human neoplasms. However, limited data exist on the role of COX-2 in follicular carcinomas of the thyroid. Studies in this area are potentially significant, since therapeutic agents that inhibit COX-2 are currently available and could play a role in treatment. Design.—A retrospective clinicopathologic review with COX-2 immunohistochemical staining of 34 follicular carcinomas and 7 follicular adenomas with incomplete capsular penetration was performed. Results.—The study included 41 patients (25 women; mean age, 50.9 years). All patients underwent gross total resection of the neoplasm. Fifteen carcinoma patients received adjuvant radiotherapy. Seven patients with follicular carcinomas developed recurrent disease: 3 patients were alive (mean follow-up, 10.1 years) and 4 patients died of metastatic disease (mean follow-up, 3.5 years). All remaining patients were disease free (mean follow-up, 5.9 years). Only 1 follicular adenoma with incomplete capsular penetration recurred (patient alive at 9 years). The remaining patients were disease free (mean follow-up, 4.9 years). The COX-2 staining was positive in 11 tumors (9 of 34 follicular carcinomas, 2 of 7 follicular adenomas with incomplete capsular penetration). A greater percentage of recurrences (36% COX-2 positive vs 13% COX-2 negative) and fatal tumors (18% COX-2 positive vs 7% COX-2 negative) occurred in patients who had COX-2–positive staining neoplasms. Conclusion.—Only a few follicular carcinomas (26%) and follicular adenomas with incomplete capsular penetration (29%) express COX-2 by immunohistochemical analysis. The data suggest that such expression of COX-2 may correlate with increased tumor recurrence and death; however, studies with larger numbers of patients will be needed to establish this.

scholarly journals Streptococcus suis Induces Expression of Cyclooxygenase-2 in Porcine Lung Tissue

2021 ◽  
Vol 9 (2) ◽  
pp. 366
Author(s):  
Muriel Dresen ◽  
Josephine Schenk ◽  
Yenehiwot Berhanu Weldearegay ◽  
Désirée Vötsch ◽  
Wolfgang Baumgärtner ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Streptococcus Suis ◽  
Cyclooxygenase 2 ◽  
Economic Losses ◽  
Biological Processes ◽  
Alveolar Tissue ◽  
Cox 2 ◽  
Ciliated Epithelial Cells ◽  
Immunohistological Analysis

Streptococcus suis is a common pathogen colonising the respiratory tract of pigs. It can cause meningitis, sepsis and pneumonia leading to economic losses in the pig industry worldwide. Cyclooxygenase-2 (COX-2) and its metabolites play an important regulatory role in different biological processes like inflammation modulation and immune activation. In this report we analysed the induction of COX-2 and the production of its metabolite prostaglandin E2 (PGE2) in a porcine precision-cut lung slice (PCLS) model. Using Western blot analysis, we found a time-dependent induction of COX-2 in the infected tissue resulting in increased PGE2 levels. Immunohistological analysis revealed a strong COX-2 expression in the proximity of the bronchioles between the ciliated epithelial cells and the adjacent alveolar tissue. The morphology, location and vimentin staining suggested that these cells are subepithelial bronchial fibroblasts. Furthermore, we showed that COX-2 expression as well as PGE2 production was detected following infection with two prevalent S. suis serotypes and that the pore-forming toxin suilysin played an important role in this process. Therefore, this study provides new insights in the response of porcine lung cells to S. suis infections and serves as a basis for further studies to define the role of COX-2 and its metabolites in the inflammatory response in porcine lung tissue during infections with S. suis.

scholarly journals The role of cyclooxygenase-2 on endurance exercise training in female LDL-receptor knockout ovariectomized mice

2013 ◽  
Vol 85 (3) ◽  
pp. 1157-1164 ◽  
Author(s):  
FLAVIA DE OLIVEIRA ◽  
LAURA B.M. MAIFRINO ◽  
GUSTAVO P.P. DE JESUS ◽  
JULIANA G. CARVALHO ◽  
CLAUDIA MARCHON ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Exercise Training ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Cyclooxygenase 2 ◽  
Sedentary Control ◽  
Down Regulation ◽  
Ovariectomized Mice ◽  
Cox 2

Estrogen deprivation in postmenopausal women increases cardiovascular risk. Cardiovascular risk as a result of atherosclerosis is able to induce an inflammatory disease as far as cyclooxygenase-2 ( COX-2) expression. The purpose of the study was to investigate the role of COX-2 on exercise training in female mice low-density lipoprotein receptor knockout ( LDL-KO) with or without ovariectomy. A total of 15 female C57BL/6 mice and 15 female LDL-KO mice were distributed into 6 groups: sedentary control, sedentary control ovariectomized, trained control ovariectomized, LDL-KO sedentary, LDL-KO sedentary ovariectomized and LDL-KO trained ovariectomized. The ascending part of the aorta was stained with H&E and COX-2 expression was assessed by immunohistochemistry. Results revealed that ovariectomy as well as exercise training were not able to induce histopathological changes in mouse aorta for all groups investigated. LDL-KO mice demonstrated plaque containing cholesterol clefts, foamy histiocytes and mild inflammatory process for all groups indistinctly. Ovariectomy induced a strong immunoexpression in atherosclerosis lesion of LDL-KO mice. Nevertheless, a down-regulation of COX-2 expression was detected in LDL-KO trained ovariectomized when compared to LDL-KO sedentary. Our results are consistent with the notion that exercise training is able to modulate COX-2 expression in LDL-KO mice as a result of COX-2 down-regulation.

scholarly journals The Role of Propolis in Pulp Pain by Inhibiting Cyclooxygenase-2 Expression

2021 ◽  
Vol 11 (1) ◽  
pp. 11
Author(s):  
Ira Widjiastuti ◽  
Widya Saraswati ◽  
Annisa Rahma
Keyword(s):  
Side Effects ◽  
Pain Relief ◽  
Inflammatory Pain ◽  
Cyclooxygenase 2 ◽  
Propolis Extract ◽  
In Silico Studies ◽  
Cox 2

Background: Inflammation of the pulp can lead to elicit pain. Pain in inflammation is induced by the cyclooxygenase-2 enzyme (COX-2) which induces prostaglandin E2 (PGE2) resulting in pain. Pain in the pulp can be relieved by eugenol. In its application, eugenol is toxic to pulp fibroblasts. Due to the side effect, it is worth considering other biocompatible materials with minimal side effects, such as propolis. Flavonoids and phenolic acids that contained in propolis can inhibit COX-2. Therefore, an analysis outlined in the literature review is needed to examine the results of research related to the role of propolis as pulp pain relief by inhibiting COX-2 expression. Purpose: To analyze the role of propolis in pulp pain by inhibiting COX-2 expression. Reviews: Propolis extract that extracted by ethanol, water, and hydroalcohol has pain relief properties in the pulp by inhibiting COX-2 by directly binding to the COX-2 receptors and by reducing the production of proinflammatory cytokines which are COX-2 inducers, proven through in vivo, in vitro, and in silico studies in various target cell organs. Conclusion: Propolis extract has high prospect as inflammatory pain inhibitor in the pulp by inhibit COX-2 expression.

Role of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) derived prostaglandins (PG) in adaptive cytoprotection induced by mild stress

1998 ◽  
Vol 114 ◽  
pp. A82
Author(s):  
T. Brzozowski ◽  
P.C. Konturek ◽  
R. Pajdo ◽  
N. Nagraba ◽  
A. Szczeklik ◽  
...  
Keyword(s):  
Cyclooxygenase 2 ◽  
Mild Stress ◽  
Adaptive Cytoprotection ◽  
Cyclooxygenase 1 ◽  
Cox 2 ◽  
Cox 1

A role for cyclooxygenase-2 in lipopolysaccharide-induced anorexia in rats

2002 ◽  
Vol 283 (4) ◽  
pp. R862-R868 ◽  
Author(s):  
F. Lugarini ◽  
B. J. Hrupka ◽  
G. J. Schwartz ◽  
C. R. Plata-Salaman ◽  
W. Langhans
Keyword(s):  
Cerebrospinal Fluid ◽  
Cyclooxygenase 2 ◽  
Major Metabolite ◽  
Time Dependent ◽  
Selective Inhibitors ◽  
Cox 2 ◽  
Cox 1

Because nonselective cycloooxygenase (COX) inhibition attenuated anorexia after lipopolysaccharide (LPS) administration, we tested the ability of resveratrol (2.5, 10, and 40 mg/kg) and NS-398 (2.5, 10, and 40 mg/kg), selective inhibitors of the two COX isoforms COX-1 and -2, respectively, to attenuate LPS (100 μg/kg ip)-induced anorexia. NS-398 (10 and 40 mg/kg) administered with LPS at lights out attenuated LPS-induced anorexia, whereas resveratrol at all doses tested did not. Because prostaglandin (PG) E2 is considered the major metabolite synthesized by COX, we measured plasma and cerebrospinal fluid (CSF) PGE2levels after LPS administration. LPS induced a time-dependent increase of PGE2 in CSF but not in plasma. NS-398 (5, 10, and 40 mg/kg) blocked the LPS-induced increase in CSF PGE2, whereas resveratrol (10 mg/kg) did not. These results support a role of COX-2 in mediating the anorectic response to peripheral LPS and point at PGE2 as a potential neuromodulator involved in this response.

Cyclooxygenase-2 expression in Warthin's tumour

2005 ◽  
Vol 119 (7) ◽  
pp. 515-518 ◽  
Author(s):  
A H C Loy ◽  
T C Putti ◽  
L K S Tan
Keyword(s):  
Quantitative Analysis ◽  
Parotid Gland ◽  
Immunohistochemical Staining ◽  
Cyclooxygenase 2 ◽  
Duct System ◽  
Salivary Duct ◽  
Epithelial Component ◽  
Warthin’S Tumour ◽  
Cox 2

Objectives: To determine whether cyclooxygenase-2 (COX-2) is overexpressed in Warthin's tumours, and to characterize its pattern of expression.Methods: Twenty-one paraffin-embedded Warthin's tumour specimens were analysed by immunohistochemical staining for expression of human COX-2. Semi-quantitative analysis of the staining was performed.Results: In all of the specimens, we found that there was overexpression of COX-2 within the epithelial component of the tumours, with no expression in the lymphoid components. There was also overexpression of COX-2 in the salivary duct system of normal parotid tissue.Conclusions: Our results suggest that COX-2 is up-regulated in the epithelial component of Warthin's tumours. Our findings support the hypothesis that Warthin's tumours originate from heterotopic ductal epithelial cells of the parotid gland. The role of COX-2 expression in the pathogenesis of Warthin's tumours remains to be determined.

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