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J Pharm Pharmacol ; 76(7): 788-797, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38538077

RESUMEN

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.


Asunto(s)
Aminobutiratos , Compuestos de Bifenilo , Combinación de Medicamentos , Interleucina-6 , Ratas Wistar , Daño por Reperfusión , Factor de Transcripción STAT1 , Transducción de Señal , Tetrazoles , Valsartán , Animales , Masculino , Valsartán/farmacología , Interleucina-6/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Ratas , Compuestos de Bifenilo/farmacología , Tetrazoles/farmacología , Aminobutiratos/farmacología , Transducción de Señal/efectos de los fármacos , Factor de Transcripción STAT1/metabolismo , Antioxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Malondialdehído/metabolismo , Modelos Animales de Enfermedad , Angiotensina II , Apoptosis/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Intestinos/efectos de los fármacos , Caspasa 3/metabolismo
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