Casuarinin modulates renin-angiotensin-aldosterone system to counter ephedrine-induced myocardial damage in rats.

IF 2.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon Pub Date : 2025-11-01 Epub Date: 2025-08-06 DOI:10.1016/j.toxicon.2025.108522

Hesham M Hassan, Muhammad Faisal Hayat, Ali Akbar, Azka Zafar, Khalid J Alzahrani, Fuad M Alzahrani, Abrar Aljohani

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引用次数: 0

Abstract

Ephedrine (EPH) is a sympathomimetic drug that showed adverse effects on different body organs such as heart. Casuarinin (CAS) is a polyphenolic agent that exhibits various biological as well as pharmacological properties. The current research was performed to explore the mitigative attributes of CAS against EPH instigated sub-chronic cardiotoxicity. Thirty-six Sprague Dawley male rats were divided into control, EPH (20 mgkg^-1), CAS (25 mgkg^-1) + EPH (20 mgkg^-1), and CAS (20 mgkg^-1) alone administered group. Our findings revealed that EPH exposure provoked the gene expression of renin (REN), angiotensinogen (AGT), angiotensin I (Ang I), angiotensin II (Ang II), angiotensin II receptor type 1 (AGTR1), aldosterone synthase (CYP11B2), and mineralocorticoid receptor (NR3C2). The enzymatic activities of heme-oxygenase-1 (HO-1), glutathione peroxidase (GPx) (54.30 %), superoxide dismutase (SOD) (62.38 %), glutathione reductase (GSR) (54.80 %), catalase (CAT) (67.54 %), glutathione (GSH) (62.14 %) and glutathione S-transferase (GST) (44.25 %) were suppressed while the concentrations of reactive oxygen species (ROS) (2518.52 %) and malondialdehyde (MDA) (2654.55 %) were provoked after EPH intoxication. Besides, the EPH exposure exacerbated the concentration of N-terminal pro-B-type natriuretic peptide (ProBNP) (179.39), creatine kinase-myocardial band (CK-MB) (133.55 %), creatine phosphokinase (CPK) (180.72 %), C-reactive protein (CRP) (348.34 %), troponin-T (TnT) (1210.91 %), lactate dehydrogenase (LDH) (518.47 %), troponin-I (TnI) (1266.67 %) and brain natriuretic peptide (BNP) (243.34 %). The expression of Bax, and Caspase-3 were augmented while the expression of Bcl-2 was diminished after EPH administration. Moreover, EPH escalates the levels of interleukin-1beta (IL-1β) (471.71 %), cyclooxygenase-2 (COX-2) (304.16 %), tumor necrosis factor-alpha (TNF-α) (219.96 %), interleukin-6 (IL-6) (316.76 %), and nuclear factor-kappa B (NF-κB) (343.59 %) as well as significantly (p < 0.05) dysregulated the normal histology of cardiac tissues. Nevertheless, CAS treatment notably alleviated EPH instigated sub-chronic cardiac damage through the regulation of RAAS, oxidative stress, apoptosis, and inflammation. These findings suggest that CAS could be employed as cardioprotective agent against EPH intoxication.

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木麻黄素调节肾素-血管紧张素-醛固酮系统对抗麻黄素诱发的大鼠心肌损伤

麻黄碱（Ephedrine， EPH）是一种拟交感神经药物，对心脏等不同器官有不良反应。木麻黄素（CAS）是一种多酚类药物，具有多种生物学和药理特性。本研究旨在探讨CAS对EPH诱导的亚慢性毒性的缓解作用。将36只雄性大鼠分为对照组、EPH （20 mgkg-1）组、CAS (25 mgkg-1) + EPH （20 mgkg-1）组和CAS （20 mgkg-1）单独给药组。结果显示，EPH暴露可引起肾素（REN）、血管紧张素原（AGT）、血管紧张素I （Ang I）、血管紧张素II （Ang II）、血管紧张素II受体1型（AGTR1）、醛固酮合成酶（CYP11B2）和矿化皮质激素受体（NR3C2）的基因表达。EPH中毒后，血红素加氧酶-1 （HO-1）、谷胱甘肽过氧化物酶（GPx）（54.30%）、超氧化物歧化酶（SOD）（62.38%）、谷胱甘肽还原酶（GSR）（54.80%）、过氧化氢酶（CAT）（67.54%）、谷胱甘肽（GSH）（62.14%）和谷胱甘肽s -转移酶（GST）（44.25%）活性受到抑制，活性氧（ROS）（2518.52%）和谷胱甘肽s -转移酶（MDA）（2654.55%）浓度升高。EPH暴露使n端前b型利钠肽（ProBNP）（179.39）、肌酸激酶-心肌带（CK-MB）（133.55%）、肌酸磷酸激酶（CPK）（180.72%）、c反应蛋白（CRP）（348.34%）、肌钙蛋白-t (TnT)（1210.91%）、乳酸脱氢酶（LDH）（518.47%）、肌钙蛋白- i (TnI)（1266.67%）和脑利钠肽（BNP）（243.34%）浓度升高。EPH作用后，Bax、Caspase-3表达增强，Bcl-2表达减弱。EPH使白细胞介素-1β (IL-1β)（471.71%）、环氧化酶-2 (COX-2)（304.16%）、肿瘤坏死因子-α (TNF-α)（219.96%）、白细胞介素-6 (IL-6)（316.76%）、核因子-κB (NF-κB)（343.59%）水平升高，并显著（p < 0.05）调节心脏组织正常组织学。然而，CAS治疗通过调节RAAS、氧化应激、细胞凋亡和炎症显著减轻EPH引起的亚慢性心脏损伤。这些结果提示CAS可作为EPH中毒的心脏保护剂。

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来源期刊

Toxicon 医学-毒理学

CiteScore

4.80

自引率

10.70%

发文量

358

审稿时长

68 days

期刊介绍： Toxicon has an open access mirror Toxicon: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. An introductory offer Toxicon: X - full waiver of the Open Access fee. Toxicon''s "aims and scope" are to publish: -articles containing the results of original research on problems related to toxins derived from animals, plants and microorganisms -papers on novel findings related to the chemical, pharmacological, toxicological, and immunological properties of natural toxins -molecular biological studies of toxins and other genes from poisonous and venomous organisms that advance understanding of the role or function of toxins -clinical observations on poisoning and envenoming where a new therapeutic principle has been proposed or a decidedly superior clinical result has been obtained. -material on the use of toxins as tools in studying biological processes and material on subjects related to venom and antivenom problems. -articles on the translational application of toxins, for example as drugs and insecticides -epidemiological studies on envenoming or poisoning, so long as they highlight a previously unrecognised medical problem or provide insight into the prevention or medical treatment of envenoming or poisoning. Retrospective surveys of hospital records, especially those lacking species identification, will not be considered for publication. Properly designed prospective community-based surveys are strongly encouraged. -articles describing well-known activities of venoms, such as antibacterial, anticancer, and analgesic activities of arachnid venoms, without any attempt to define the mechanism of action or purify the active component, will not be considered for publication in Toxicon. -review articles on problems related to toxinology. To encourage the exchange of ideas, sections of the journal may be devoted to Short Communications, Letters to the Editor and activities of the affiliated societies.