Betaine alleviates methomyl-triggered oxidative stress-mediated cardiopulmonary inflammation in rats through iNOS/Cox2 and Nrf2/HO1/Keap1 signaling pathway

IF 3.3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicology and applied pharmacology Pub Date : 2025-02-01 DOI:10.1016/j.taap.2024.117223

Eman I. Hassanen , Neven H. Hassan , Ahmed M. Hussien , Marwa A. Ibrahim , Merhan E. Ali

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引用次数: 0

Abstract

Methomyl (MET), a universally used insecticide, has many adverse effects on various organs in both humans and animals including the liver, kidneys, and heart. Betaine (BET), a natural antioxidant, has a protective role against many toxicants-induced cardiovascular disorders. The present study was designed to elucidate the molecular mechanistic way underlying the mitigating effect of BET against MET-induced cardiopulmonary injury and inflammation in rats. Four groups of rats were used and orally administered the consequent materials daily for 28 days: normal saline, BET (250 mg/kg bwt), MET (2 mg/kg bwt), MET + BET. Blood and tissue (heart & lungs) samples were collected to assess the oxidative stress markers, lipid profile, biochemical markers, microscopic appearance, and inflammatory gene regulations. The results proved that MET induced oxidant/antioxidant imbalance, elevation of serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels, and deterioration in lipid profile. The histopathological inspection showed severe myocardial necrosis and interstitial pneumonia along with bronchitis and alveolar damage. There was a marked increase in the intensity of cyclooxygenase-2 (Cox-2) and inducible nitric oxide synthase (iNOS) immunostaining with marked upregulation of the transcriptase levels of keap-1gene and downregulation of nuclear factor erythroid 2-related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) genes in both heart and lung tissues of MET group. Otherwise, the coadministration of BET with MET markedly alleviated the abovementioned toxicological parameters. We can conclude that BET was able to reduce the MET-induced oxidative stress-mediated cardiovascular injury and pulmonary inflammation by modulating Keap-1/Nrf-2 signaling pathway and inactivating Cox-2 and iNOS expression which therefore reduced further cellular damage and inflammatory response.

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甜菜碱通过iNOS/Cox2和Nrf2/HO1/Keap1信号通路缓解甲多梅酰引发的氧化应激介导的大鼠心肺炎症。

灭多威（Methomyl， MET）是一种广泛使用的杀虫剂，对人类和动物的肝脏、肾脏和心脏等多种器官有许多不良影响。甜菜碱（BET）是一种天然抗氧化剂，对许多毒物引起的心血管疾病具有保护作用。本研究旨在阐明BET对met诱导的大鼠心肺损伤和炎症的缓解作用的分子机制。四组大鼠分别口服生理盐水、BET（250 mg/kg bwt）、MET（2 mg/kg bwt）、MET + BET，共28 天。收集血液和组织（心脏和肺）样本，评估氧化应激标志物、脂质谱、生化标志物、显微外观和炎症基因调控。结果表明，MET诱导氧化/抗氧化失衡，血清肌酸激酶（CK）和乳酸脱氢酶（LDH）水平升高，血脂恶化。组织病理学检查显示心肌坏死严重，间质性肺炎伴支气管炎及肺泡损伤。MET组大鼠心脏和肺组织环氧化酶-2 （Cox-2）和诱导型一氧化氮合酶（iNOS）免疫染色强度显著升高，keep -1基因转录酶水平显著上调，核因子-红细胞2相关因子-2 （Nrf-2）和血红素加氧酶-1 （HO-1）基因表达下调。此外，BET与MET联合用药可显著缓解上述毒理学指标。由此可见，BET可以通过调节Keap-1/Nrf-2信号通路，灭活Cox-2和iNOS表达，从而减少met诱导的氧化应激介导的心血管损伤和肺部炎症，从而进一步减少细胞损伤和炎症反应。

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来源期刊

Toxicology and applied pharmacology 医学-毒理学

CiteScore

6.80

自引率

2.60%

发文量

309

审稿时长

32 days

期刊介绍： Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.