Alamandin and especially melatonin attenuate pulmonary arterial hypertension induced by monocrotalin

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology Pub Date : 2024-08-11 DOI:10.1111/fcp.13033

Seyhan Ayik, Mehmet Gunata, Onural Ozhan, Azibe Yildiz, Nigar Vardi, Emre Sonmez, Necip Ermis, Nilay Ates, Ertugrul Kilic, Samir Abbas Ali Noma, Ahmet Ulu, Seyfullah Taha Inan, Haci Ahmet Acet, Hakan Parlakpinar

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Abstract

Background

Despite the available treatments, pulmonary arterial hypertension (PAH) prognosis is poor.

Objectives

We aimed to investigate the effects of the alamandine (ALA), melatonin (MEL), and ALA + MEL in PAH.

Methods

The rats were randomly divided into Control (n = 10), monocrotaline (MCT) (n = 12), ALA (n = 12), MEL (n = 12), and ALA + MEL (n = 12) groups. PAH was induced by MCT. The ALA, MEL, and ALA + MEL groups received 50 μg/kg/day ALA, 10 mg/kg/day MEL, and ALA + MEL, respectively, for 35 days. Echocardiographic and hemodynamic measurements and tissue analyses (morphometric, histopathological, ELISA, and western blot) were performed.

Results

Monotherapies, especially MEL, reduced the right ventricular (RV) systolic pressure. Only MEL increased the pulmonary artery acceleration time. MCT increased the RV/left ventricle (LV) + interventricular septum (IVS) ratio. While ALA and ALA + MEL slightly decreased the RV/(LV + IVS), MEL significantly restored it. MCT increased the tunica intima-media (TIM) thickness, PCNA and α-SMA of pulmonary arterioles, histopathological score (HS) (inflammatory infiltration etc.) of the lung, and RV. All treatments reduced the TIM thickness (especially MEL), PCNA, and α-SMA. All treatments significantly decreased the HS of the lung; however, MEL and ALA + MEL produced greater benefits. All treatments attenuated the HS of RV. MCT caused a significant increase in lung lysyl oxidase (LOX) activity. All treatments restored the LOX; however, MEL and ALA + MEL provided greater improvement. While lung Nrf-2 was increased in MCT-treated rats, MEL reduced it.

Conclusion

ALA, MEL, and ALA + MEL attenuate PAH and protect RV via antiproliferative, anti-remodeling, antihypertrophic, anti-inflammatory, and free radical scavenging (only MEL) capabilities. Overall, MEL produced the best outcomes.

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阿拉曼丁，尤其是褪黑素可减轻单核细胞增多症诱发的肺动脉高压。

背景：尽管有治疗方法，但肺动脉高压（PAH）的预后很差：尽管有多种治疗方法，但肺动脉高压（PAH）的预后很差：我们旨在研究阿拉曼定（ALA）、褪黑素（MEL）以及 ALA + MEL 对 PAH 的影响：方法：将大鼠随机分为对照组（n = 10）、一缩醛（MCT）组（n = 12）、ALA 组（n = 12）、MEL 组（n = 12）和 ALA + MEL 组（n = 12）。MCT诱导PAH。ALA组、MEL组和ALA + MEL组分别接受50微克/千克/天的ALA、10毫克/千克/天的MEL和ALA + MEL，共35天。进行了超声心动图和血液动力学测量以及组织分析（形态计量学、组织病理学、ELISA和Western印迹）：结果：单一疗法，尤其是 MEL，降低了右心室收缩压。只有 MEL 增加了肺动脉加速时间。MCT 增加了 RV/ 左心室（LV）+ 室间隔（IVS）比率。虽然 ALA 和 ALA + MEL 稍微降低了 RV/（LV + IVS），但 MEL 显著恢复了这一比率。MCT 增加了肺动脉内膜厚度、PCNA 和 α-SMA、肺组织病理学评分（HS）（炎症浸润等）和 RV。所有治疗方法都能减少 TIM 厚度（尤其是 MEL）、PCNA 和 α-SMA。所有治疗方法都能明显降低肺的HS，但MEL和ALA + MEL的疗效更好。所有治疗方法都减轻了 RV 的 HS。MCT 导致肺溶酶体氧化酶（LOX）活性明显增加。所有治疗方法都能恢复 LOX，但 MEL 和 ALA + MEL 的改善效果更好。MCT 处理的大鼠肺部 Nrf-2 增加，而 MEL 则减少：结论：ALA、MEL 和 ALA + MEL 可通过抗增殖、抗重塑、抗肥大、抗炎和清除自由基（仅 MEL）的能力减轻 PAH 并保护 RV。总体而言，MEL 的效果最好。

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

Fundamental & Clinical Pharmacology 医学-药学

CiteScore

5.30

自引率

6.90%

发文量

111

审稿时长

6-12 weeks

期刊介绍： Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.