Investigation of metabolite profiles of kidney tissues in rats treated with favipiravir drug: An NMR-based metabolomics study.

IF 3.1 3区 医学 Q2 CHEMISTRY, ANALYTICAL Journal of pharmaceutical and biomedical analysis Pub Date : 2025-03-15 Epub Date: 2024-12-16 DOI:10.1016/j.jpba.2024.116640
Zeynep Rozerin Çevik, Ali Erdoğan, Akın Mumcu, Berat Doğan
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Abstract

In response to the urgent need for effective treatments during the rapid spread and high mortality rate of COVID-19, existing drugs were repurposed for potential antiviral effects, including favipiravir, originally designed as an RNA-dependent RNA polymerase inhibitor for influenza. Despite limited antiviral effectiveness against COVID-19, favipiravir has been reported to cause several adverse drug events (ADEs) in the body. Recent studies have shown that favipiravir can damage various tissues in rats. However, a detailed analysis of its effects on the metabolomics profile of tissues using high-resolution spectroscopic technologies has not yet been conducted. In this study, it was aimed to analyze the metabolomic changes in rat kidney tissues induced by favipiravir, using high-resolution nuclear magnetic resonance (NMR) spectroscopy. Sixty male Wistar Albino rats were randomly divided into three groups: control, low-dose favipiravir (200 mg/kg), and high-dose favipiravir (300 mg/kg), with 20 rats per group. Each group received its respective treatment via oral gavage. After the treatment period, kidney tissue samples were collected and subjected to 1H NMR analysis. Bioinformatics analysis of the obtained 1H NMR spectra suggests that favipiravir induces dose-dependent metabolic changes in kidney tissue, with higher doses causing more profound disruptions in several pathways.

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favipiravir药物治疗大鼠肾脏组织代谢物谱的研究:基于核磁共振的代谢组学研究。
为了应对COVID-19快速传播和高死亡率期间对有效治疗的迫切需求,现有药物被重新利用以发挥潜在的抗病毒作用,包括最初设计为RNA依赖性RNA聚合酶流感抑制剂的favipiravir。尽管对COVID-19的抗病毒效果有限,但据报道,favipiravir会在体内引起几种药物不良事件(ADEs)。最近的研究表明,法匹拉韦可以损害大鼠的多种组织。然而,尚未使用高分辨率光谱技术详细分析其对组织代谢组学特征的影响。本研究旨在利用高分辨率核磁共振(NMR)技术分析favipiravir诱导的大鼠肾脏组织代谢组学变化。选择雄性Wistar Albino大鼠60只,随机分为对照组、低剂量favipiravir(200 mg/kg)和高剂量favipiravir(300 mg/kg) 3组,每组20只。各组分别给予灌胃治疗。治疗期结束后,收集肾组织样本,进行1H NMR分析。对获得的1H NMR谱的生物信息学分析表明,favipiravir在肾组织中诱导剂量依赖性代谢变化,高剂量对几种途径造成更严重的破坏。
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来源期刊
CiteScore
6.70
自引率
5.90%
发文量
588
审稿时长
37 days
期刊介绍: This journal is an international medium directed towards the needs of academic, clinical, government and industrial analysis by publishing original research reports and critical reviews on pharmaceutical and biomedical analysis. It covers the interdisciplinary aspects of analysis in the pharmaceutical, biomedical and clinical sciences, including developments in analytical methodology, instrumentation, computation and interpretation. Submissions on novel applications focusing on drug purity and stability studies, pharmacokinetics, therapeutic monitoring, metabolic profiling; drug-related aspects of analytical biochemistry and forensic toxicology; quality assurance in the pharmaceutical industry are also welcome. Studies from areas of well established and poorly selective methods, such as UV-VIS spectrophotometry (including derivative and multi-wavelength measurements), basic electroanalytical (potentiometric, polarographic and voltammetric) methods, fluorimetry, flow-injection analysis, etc. are accepted for publication in exceptional cases only, if a unique and substantial advantage over presently known systems is demonstrated. The same applies to the assay of simple drug formulations by any kind of methods and the determination of drugs in biological samples based merely on spiked samples. Drug purity/stability studies should contain information on the structure elucidation of the impurities/degradants.
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