Sacubitril/valsartan protective effect on induced intestinal ischemia/reperfusion injury via immune modulation of IL6/STAT1 pathway.

IF 2.8 4区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of Pharmacy and Pharmacology Pub Date : 2024-07-05 DOI:10.1093/jpp/rgae031

Marwa Monier Mahmoud Refaie, Entesar Farghly Amin, Marwa Nadi Hassan, Rehab Ahmed Rifaai, Asmaa M A Bayoumi, Maha Yehia Kamel

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引用次数: 0

Abstract

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.

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萨库比特利/缬沙坦通过免疫调节 IL6/STAT1 通路对诱导性肠缺血再灌注损伤的保护作用

目的：肠道缺血再灌注（IIR）是一种需要立即干预的危急情况。小肠是对肠道缺血再灌注损伤最敏感的组织之一，而且仍然是一种高发病率疾病，据报道死亡率在 30% 至 90% 之间。因此，我们旨在评估萨库比特利/缬沙坦（SAC/VAL）对IIR损伤的保护作用：方法：32 只成年雄性 Wistar 大鼠被用于我们的模型，并分为四组：假组、SAC/VAL 治疗组（不含 IIR）、IIR 组和 SAC/VAL 治疗组（含 IIR）。在诱导 IIR 前口服 30 mg/kg 剂量的 SAC/VAL：主要发现：SAC/VAL能明显改善IIR诱导的变化，因为它能降低丙二醛（MDA）、肿瘤坏死因子α（TNFα）、血管紧张素Ⅱ（ANGⅡ）、白细胞介素6（IL 6）、活性Caspase 3和转录信号转导和激活因子（STAT1）。然而，服用 SAC/VAL 能明显提高抗氧化参数，如总抗氧化能力（TAC）、超氧化物歧化酶（SOD）和还原型谷胱甘肽（GSH）。此外，在 IIR 组中观察到的组织学结构改变在 SAC/VAL 的作用下得到了改善：结论：SAC/VAL可通过调节肾素血管紧张素醛固酮系统、抗氧化、抗凋亡、抗炎和调节IL6/STAT1通路来预防IIR诱导的损伤。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Pharmacy and Pharmacology 医学-药学

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： JPP keeps pace with new research on how drug action may be optimized by new technologies, and attention is given to understanding and improving drug interactions in the body. At the same time, the journal maintains its established and well-respected core strengths in areas such as pharmaceutics and drug delivery, experimental and clinical pharmacology, biopharmaceutics and drug disposition, and drugs from natural sources. JPP publishes at least one special issue on a topical theme each year.