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.
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.
Physical exercise prior to myocardial infarction (MI) protects against the IM scar, prevents cardiac remodeling and attenuates systolic dysfunction and diastolic activity in rats. Evaluate the influence of physical training by swimming, performed prior to MI, on the growth of cardiac masses, pulmonary and hepatic water content. Characterize the echocardiographic changes indicative of cardioprotection induced by physical training prior to myocardial infarction. Young rats weighing between 170 and 190 grams, from the Experimental Models Development Center (CEDEME) of the Federal University of São Paulo, were used. The animals were kept in boxes with water and rations in a temperature controlled environment. They were distributed in four experimental groups: non‐infarcted sedentary (SS); Sedentary infarcted (IMS); Trained non‐infarcted (SE); Infarcted Training (IME) The animals were submitted to a period of adaptation to the swimming exercise, later those belonging to the SE and IME groups swam for 90 minutes, this time was maintained until five weeks were completed. After this period the maximum physical capacity (MCF) was again evaluated and then the rats were submitted to myocardial infarction (MI) surgery. The method of production of IM was based on the work of Johns and Olson (1954). After three weeks of infarction the animals were submitted to Doppler echocardiography and were sacrificed for the analysis of the wet and dry weight of the heart, lungs and liver. The data were statistically evaluated, one‐way ANOVA followed by Tukey's test, and significant values of (p<0,05) were considered. After the training period prior to MI, the animals exercised SE (2,317 ± 275 seconds) and IME (3,104 ± 281 seconds) had an increase (p ≤ 0.001) in MCF compared to SS sedentary animals (378 ± 43 seconds) and IMS (341 ± 25 seconds), respectively. These results indicate that the protocol was effective in increasing the cardiorespiratory capacity of the exercised animals. The atrial masses of the infarcted animals were higher than those of the non‐infarcted animals (p ≤ 0.001). The right ventricular (RV) mass values of SE, IMS and IME animals were higher than the values for the SS group (p ≤ 0.001). There was hypertrophy (12%) of the left ventricle (LV) of the SE rats in relation to the SS (p = 0.008). The results of the IMS and IME groups related to the cardiac morphology indicated significant LV dilation and decreased LV wall thickness (p ≤ 0.001) in relation to SS and SE animals. No significant differences were observed in the comparisons of aortic diameters, left atrial and LV posterior wall thickness between groups. The water contents of the lungs and liver did not differ significantly between the four experimental groups. The results related to the systolic function indicated that there was a significant loss (p ≤ 0.001) of the shortening fraction and the shortening fraction of the transverse area indicating clear systolic dysfunction, not prevented by physical exercise. Values for diastolic function in infarcted animals were significantly worse than those recorded in non‐infarcted animals (p<0,05). The protocol of physical training per swimming, imposed prior to MI, did not prevent the cardiac remodeling of infarcted rats and does not prevent cardiac remodeling or systolic and diastolic dysfunction evaluated by Doppler echocardiography.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Intestinal mucositis (MI), characterized by inflammation and ulceration of the intestinal mucosa, is one of the main causes of morbidity and mortality in chemotherapy patients (LEE et al., 2014).GOALSTo evaluate the action of the white angico polysaccharide on the histological changes in villi and crypts induced by 5‐FU in the intestinal mucosa;To verify the role of the white angico polysaccharide in the involvement of the cyclooxygenase‐2 (COX‐2) pathway in the 5‐FU induced intestinal mucositis model;METHODSThe experimental protocol was forwarded and approved by the Ethics Committee for Animal Use (CEUA) of UFC (3463140518). Intestinal mucositis was induced in mice with administration of 5‐FU, according to the methodology described by Carneiro‐Filho et al. (2004), in which the mice received on the first day of the experiment a single dose of 5‐FU (450 mg/kg) via intraperitoneal (i.p). The treatment was done using three doses of the white angico polysaccharide (100, 200, 400 mg/kg) one day after the injection of 5‐FU, the doses being based on Santos et al. (2013). The animals were divided into groups: Group I (Saline): saline solution 0.9% (0.1 mL/10g) and intraperitoneal (i.p), in parallel to the other groups treated throughout the study. Group II (5‐FU): on the first day of the experimental protocol will receive a single dose of 5‐FU (450 mg/kg) i.p. and will be treated with 0.9% saline solution (0.1 mL/10g) on the next four days. Group III (Angico best dose): 5‐FU (450 mg/kg) i.p on the first day of the experiment and was treated with angico diluted in distilled water. Group IV (Celecoxib): single dose of 5‐FU (450mg/kg) intraperitoneally (i.p) on the first day. On the following days of the experimental protocol only Celecoxib (7.5 mg/kg, i.p) was administered Group V (Celocoxib + Angico best dose): single dose of 5‐FU (450mg/kg) intraperitoneally (i.p) on the first day. On the second day of protocol, they was received white angico polysaccharide diluted in distilled water, and Celecoxib (7.5 mg/kg, i.p). After the histological processing, the morphometric evaluation was carried out with the aid of the ImageJ software, where the height of the villi and the depth of the crypts were measured. Immunohistochemistry for COX‐2 was then performed using the streptavidin‐biotin‐peroxidase method (HSU; RAINE, 1981)RRESULTSThe white Angico polysaccharide was able to statistically (p <0.05) prevent the shortening of villi and decrease the depth of the crypts caused by 5‐FU (Figure 1). The groups treated with angio 400 mg/kg, CLX and the CLX + angio combination (Figure 2) showed a statistically significant (p <0.05) reduction of the immunolabelled area for COX‐2 when compared to the 5‐FU group.CONCLUSIONThe white angico polysaccharide protected the intestinal mucosa and promoted a decrease in COX‐2 expression in the 5‐FU induced intestinal mucositis model.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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