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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引用次数: 0

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.

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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.