Sildenafil abrogates radiation-induced hepatotoxicity in animal model: The impact of NF-κB-p65, P53, Nrf2, and SIRT 1 pathway

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology Pub Date : 2025-03-12 DOI:10.1016/j.fct.2025.115373

Waleed A.I. Khallaf , Abd Elmoneim A.H. Taha , Ahmed S. Ahmed , Mohamed I.A. Hassan , Amira M. Abo-youssef , Ramadan A.M. Hemeida

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Abstract

Ionizing radiation has both beneficial and harmful effects on human health, prompting researchers to find ways to protect organs from its adverse impacts. Sildenafil (SIL) has gained attention in protective medicine due to its antioxidant, anti-inflammatory, and anti-apoptotic properties.

Aim

This study aimed to investigate SIL's protective mechanisms against radiation-induced liver damage.

Method

Forty adult male Wistar rats were divided into: control group, SIL group (2.5 mg/kg,p.o), irradiation group (rats were exposed to single shot at a dose of 10 Gy to induce liver damage), and SIL + irradiation group. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were evaluated. Liver samples were used to evaluate oxidative stress indicators, reduced glutathione (GSH), malondialdehyde (MDA), nitric oxide(NO), Hepatic antioxidant nuclear factor erythroid 2-related factor 2(Nrf2), and apoptoticp53 upregulated modulator of apoptosis(P53) gene expression were determined by Western blot analysis. Immunohistochemical analysis for hepatic nuclear factor-kappa B (NF-κB) and silent information regulator-1(SIRT1) were performed along with histopathological examination.

Results

SIL effectively diminished inflammation by reducing p–NF–κB-p65 and increasing Nrf2 and SIRT 1 expression. Additionally, SIL restrained apoptosis by reducing P53 protein expressions. Moreover, SIL significantly improved radiation-induced histopathological changes.

Significance

SIL preventing hepatotoxicity associated with radiation exposure.

Abstract Image

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在动物模型中，西地那非消除辐射引起的肝毒性：NF-κB-p65、P53、Nrf2和sirt1通路的影响。

电离辐射对人体健康既有有益的影响，也有有害的影响，促使研究人员寻找保护器官免受其不利影响的方法。西地那非（Sildenafil， SIL）因其抗氧化、抗炎、抗细胞凋亡等特性在保护医学领域受到广泛关注。目的：探讨SIL对放射性肝损伤的保护机制。方法：将40只成年雄性Wistar大鼠分为：对照组、SIL组（2.5mg/kg,p.o）、照射组（10 Gy单次照射致肝损伤）和SIL+照射组。测定血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）和碱性磷酸酶（ALP）水平。采用肝脏样品评价氧化应激指标，采用Western blot法检测还原谷胱甘肽（GSH）、丙二醛（MDA）、一氧化氮（NO）、肝抗氧化核因子红系2相关因子2（Nrf2）、凋亡调质因子P53 （P53）基因表达。免疫组化分析肝核因子-κB （NF-κB）和沉默信息调控因子-1（SIRT1）并进行组织病理学检查。结果：SIL通过降低p-NF-κB-p65，增加Nrf2和sirt1的表达，有效减轻炎症反应。此外，SIL通过降低P53蛋白表达抑制细胞凋亡。此外，SIL可显著改善放射诱导的组织病理改变。意义：SIL可预防与辐射暴露相关的肝毒性。

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

Food and Chemical Toxicology 工程技术-毒理学

CiteScore

10.90

自引率

4.70%

发文量

651

审稿时长

31 days

期刊介绍： Food and Chemical Toxicology (FCT), an internationally renowned journal, that publishes original research articles and reviews on toxic effects, in animals and humans, of natural or synthetic chemicals occurring in the human environment with particular emphasis on food, drugs, and chemicals, including agricultural and industrial safety, and consumer product safety. Areas such as safety evaluation of novel foods and ingredients, biotechnologically-derived products, and nanomaterials are included in the scope of the journal. FCT also encourages submission of papers on inter-relationships between nutrition and toxicology and on in vitro techniques, particularly those fostering the 3 Rs. The principal aim of the journal is to publish high impact, scholarly work and to serve as a multidisciplinary forum for research in toxicology. Papers submitted will be judged on the basis of scientific originality and contribution to the field, quality and subject matter. Studies should address at least one of the following: -Adverse physiological/biochemical, or pathological changes induced by specific defined substances -New techniques for assessing potential toxicity, including molecular biology -Mechanisms underlying toxic phenomena -Toxicological examinations of specific chemicals or consumer products, both those showing adverse effects and those demonstrating safety, that meet current standards of scientific acceptability. Authors must clearly and briefly identify what novel toxic effect (s) or toxic mechanism (s) of the chemical are being reported and what their significance is in the abstract. Furthermore, sufficient doses should be included in order to provide information on NOAEL/LOAEL values.