Isorhamnetin Protects Against Organophosphate-Induced Cardiac Damage in Wistar Rats Through Redox Balance and Nrf2/HO-1 Signalling

IF 3.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Basic & Clinical Pharmacology & Toxicology Pub Date : 2026-02-24 DOI:10.1111/bcpt.70197

Yousra Bseiso, Badriyah S. Alotaibi, Alaa A. A. Aljabali, Omar Gammoh, Muna Oqal, Mohammad E. Rabeh, Ahmad M. Rabi, Esam Qnais, Abdelrahim Alqudah

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引用次数: 0

Abstract

Background

Chlorpyrifos (CPF) triggers cardiotoxicity associated with oxidative stress, inflammation and apoptosis. This study investigated whether isorhamnetin, a chemically defined flavonol (3′-O-methylquercetin, C₁₆H₁₂O₇, purity ≥ 98%), could mitigate CPF-induced myocardial injury.

Methods

Male Wistar rats were randomly divided into control, isorhamnetin, CPF and CPF + isorhamnetin groups. Cardiac biomarkers, oxidative/antioxidant status, and inflammatory and apoptotic mediators in conjunction with histopathology and Nrf2/HO-1 signalization were assessed.

Results

CPF elevated serum cTnI, CK-MB and LDH (p < 0.001), attaining lower levels after isorhamnetin cotreatment (p < 0.001). TBARS and NO were elevated (p < 0.001), whereas GSH, SOD, catalase and GPx decreased (p < 0.001) after CPF exposure; these indices were reverted with isorhamnetin. CPF increased the expression levels of NF-κB p65, TNF-α, IL-6 and IL-1β proteins and decreased that of IL-10 (p < 0.001), whereas isorhamnetin offset these effects (p < 0.001). Apoptosis was apparent with high Bax and caspase-3 and low Bcl-2 (p < 0.001); all were ameliorated by isorhamnetin. Histopathological alterations caused by CPF were ameliorated. CPF downregulated the expression and activity of Nrf2/HO-1 (p < 0.001), but this pathway was significantly induced by isorhamnetin (p < 0.001).

Conclusions

Isorhamnetin alleviates CPF-induced cardiotoxicity by restoring redox balance and modulating inflammatory and apoptotic pathways through Nrf2/HO-1 signalling.

Abstract Image

查看原文本刊更多论文

异鼠李素通过氧化还原平衡和Nrf2/HO-1信号传导保护Wistar大鼠免受有机磷诱导的心脏损伤。

背景：毒死蜱（CPF）引发与氧化应激、炎症和细胞凋亡相关的心脏毒性。本研究探讨了异鼠李素，一种化学定义的黄酮醇（3′- o -甲基槲皮素，C16H12O7，纯度≥98%）是否能减轻cpf诱导的心肌损伤。方法：雄性Wistar大鼠随机分为对照组、异鼠李素组、CPF组和CPF +异鼠李素组。评估心脏生物标志物、氧化/抗氧化状态、炎症和凋亡介质与组织病理学和Nrf2/HO-1信号的关系。结果：CPF升高血清cTnI、CK-MB和LDH (p)结论：异鼠李素通过Nrf2/HO-1信号通路，恢复氧化还原平衡，调节炎症和凋亡通路，减轻CPF诱导的心脏毒性。

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

Basic & Clinical Pharmacology & Toxicology 医学-毒理学

CiteScore

5.60

自引率

6.50%

发文量

126

审稿时长

1 months

期刊介绍： Basic & Clinical Pharmacology and Toxicology is an independent journal, publishing original scientific research in all fields of toxicology, basic and clinical pharmacology. This includes experimental animal pharmacology and toxicology and molecular (-genetic), biochemical and cellular pharmacology and toxicology. It also includes all aspects of clinical pharmacology: pharmacokinetics, pharmacodynamics, therapeutic drug monitoring, drug/drug interactions, pharmacogenetics/-genomics, pharmacoepidemiology, pharmacovigilance, pharmacoeconomics, randomized controlled clinical trials and rational pharmacotherapy. For all compounds used in the studies, the chemical constitution and composition should be known, also for natural compounds.