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J Pharm Pharmacol ; 76(7): 788-797, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38538077

RESUMO

OBJECTIVES: Intestinal ischemia reperfusion (IIR) is a critical emergency situation that needs immediate intervention. Small intestine is one of the most sensitive tissues to IR injury and it remains a highly morbid condition, with reported mortality rates ranging from 30% to 90%. Thus, we aimed to evaluate the suspected protective role of sacubitril/valsartan (SAC/VAL) on IIR injury. METHODS: Thirty-two adult male Wistar rats were used in our model and divided into four groups: sham group, SAC/VAL treated group without IIR, IIR group, and SAC/VAL treated group with IIR. SAC/VAL in a dose of 30 mg/kg was administered orally just before induction of IIR. KEY FINDINGS: SAC/VAL significantly ameliorated IIR-induced changes as it decreased malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), angiotensin II (ANG II), interleukin 6 (IL 6), active caspase 3, and signal transducer- and activator-of transcription (STAT1). However, SAC/VAL administration significantly increased antioxidant parameters such as total antioxidant capacity (TAC), superoxide dismutase (SOD), and reduced glutathione (GSH). Moreover, alteration of the histological structure was observed in IIR group that was improved by SAC/VAL. CONCLUSIONS: SAC/VAL prevents IIR-induced damage via modulation of renin angiotensin aldosterone system, antioxidant, anti-apoptotic, anti-inflammatory properties, and regulation of IL6/STAT1 pathway.


Assuntos
Aminobutiratos , Compostos de Bifenilo , Combinação de Medicamentos , Interleucina-6 , Ratos Wistar , Traumatismo por Reperfusão , Fator de Transcrição STAT1 , Transdução de Sinais , Tetrazóis , Valsartana , Animais , Masculino , Valsartana/farmacologia , Interleucina-6/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Ratos , Compostos de Bifenilo/farmacologia , Tetrazóis/farmacologia , Aminobutiratos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição STAT1/metabolismo , Antioxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Malondialdeído/metabolismo , Modelos Animais de Doenças , Angiotensina II , Apoptose/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Intestinos/efeitos dos fármacos , Caspase 3/metabolismo
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