Exploring the therapeutic potential of Modafinil in mitigating renal ischemia–reperfusion injury in rats

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology Pub Date : 2024-08-13 DOI:10.1111/fcp.13034

Fatemeh Asli, Sepideh Poshtdar, Ahmad Reza Dehpour, Razieh Mohammad Jafari

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引用次数: 0

Abstract

Background

Renal ischemia reperfusion injury (IRI) is a post-ischemic event, which can lead to subsequent acute kidney injury (AKI), transplant failure, renal dysfunction and fibrosis via heightened oxidative stress and production of inflammatory cytokines and chemokines.

Objective

This study aims to assess the effect of Modafinil, a wake-promoting agent with previously proven anti-inflammatory and anti-oxidative properties, on ameliorating renal IRI.

Methods

A total of 30 male Wistar rats were divided into five groups: Sham-operated group, ischemia reperfusion (I/R) control group and Modafinil pre-treated groups (at different doses of 50, 100 and 150 mg/kg). IRI was induced by means of bilaterally clamping the renal arteries for 45 min, followed by 24 h of reperfusion.

Results

Tissue pathological assessments demonstrated a reduction of glomerular, vascular and interstitial injury at doses of 50 and 100 mg/kg of Modafinil. The biochemical studies showed a significant decrease in tissue pro-inflammatory factors, including tumor necrosis factor alpha (TNF-α), Interleukin-18 (IL-18) and lactate dehydrogenase (LDH). Moreover, an elevation was observed in levels of super oxide dismutase (SOD) and catalase, indicating the reduction of oxidative stress. Furthermore, the levels of creatinine (Cr), urea and neutrophil gelatinase-associated lipocalin (NGAL) were declined, indicating the improvement in renal function at effective doses of Modafinil (50 and 100 mg/kg) compared to the I/R control group without Modafinil pre-treatment.

Conclusion

Our findings suggest that Modafinil holds promise as an effective therapeutic agent to address the clinical challenges associated with kidney IRI reducing the need for hospitalization and potentially alleviating related morbidities.

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探索莫达非尼缓解大鼠肾缺血再灌注损伤的治疗潜力

背景：肾缺血再灌注损伤（IRI）是一种缺血后事件，可通过加剧氧化应激和产生炎性细胞因子和趋化因子，导致随后的急性肾损伤（AKI）、移植失败、肾功能障碍和纤维化：本研究旨在评估莫达非尼对改善肾脏 IRI 的影响：方法：将 30 只雄性 Wistar 大鼠分为五组：方法：将 30 只雄性 Wistar 大鼠分为五组：假手术组、缺血再灌注（I/R）对照组和莫达非尼预处理组（50、100 和 150 毫克/千克的不同剂量）。诱导缺血再灌注的方法是双侧夹闭肾动脉45分钟，然后再灌注24小时：结果：组织病理学评估显示，莫达非尼剂量为 50 和 100 毫克/千克时，肾小球、血管和间质损伤有所减轻。生化研究显示，组织促炎因子，包括肿瘤坏死因子α（TNF-α）、白细胞介素-18（IL-18）和乳酸脱氢酶（LDH）明显减少。此外，还观察到超氧化物歧化酶（SOD）和过氧化氢酶水平升高，表明氧化应激减少。此外，肌酐（Cr）、尿素和中性粒细胞明胶酶相关脂联素（NGAL）的水平也有所下降，这表明与未经莫达非尼预处理的I/R对照组相比，有效剂量的莫达非尼（50和100毫克/千克）可改善肾功能：我们的研究结果表明，莫达非尼有望成为一种有效的治疗药物，以应对与肾脏IRI相关的临床挑战，减少住院治疗的需求，并有可能减轻相关的发病率。

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.