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Biol Pharm Bull ; 38(5): 746-52, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25947920

RESUMO

The aim of this study was to evaluate the effect of olmesartan (OLME), an angiotensin II receptor antagonist, on an intestinal mucositis model. Briefly, daily intraperitoneal (i.p.) injections of methotrexate (MTX) 7 mg/kg were administered to rats on 3 consecutive days. A subset of these rats was also pretreated with oral administration of OLME (0.5, 1.0, or 5.0 mg/kg) or vehicle as a control 30 min prior to MTX injection. Body weight, feces scoring, and death were recorded daily. On day 4, the rats were killed, and intestinal tissues were assayed for levels of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, myeloperoxidase and sucrose activity, and histopathological findings. A significant reduction in body weight was observed in the MTX+1.0 mg/kg OLME group (p<0.01). The feces scores for the MTX+0.5 mg/kg OLME and MTX+5.0 mg/kg OLME groups were also significantly higher (p<0.001). Sucrose activity was reduced in all groups treated with OLME (p<0.05). Treatment with MTX+OLM at all doses resulted in reduced inflammatory infiltration, ulcerations, vasodilation, and hemorrhagic areas (p<0.05), as well as reduced concentrations of myeloperoxidase (p<0.001). The IL-1ß and TNF-α levels were decreased in the MTX+OLME 5.0 mg/kg (p<0.01 and p<0.05, respectively) compared with the MTX-alone group. Overall, antiinflammatory activity was observed in rats with MTX-induced intestinal mucositis that were administered OLME. However, further studies are needed to elucidate the adverse effects of OLME.


Assuntos
Inflamação/prevenção & controle , Mucosa Intestinal/efeitos dos fármacos , Metotrexato/efeitos adversos , Mucosite/tratamento farmacológico , Olmesartana Medoxomila/uso terapêutico , Sacarose/metabolismo , Redução de Peso/efeitos dos fármacos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antimetabólitos Antineoplásicos/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/prevenção & controle , Modelos Animais de Doenças , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Inflamação/induzido quimicamente , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Masculino , Mucosite/induzido quimicamente , Mucosite/complicações , Neoplasias/tratamento farmacológico , Olmesartana Medoxomila/farmacologia , Ratos Wistar , Tetrazóis/farmacologia , Tetrazóis/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo
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