Chlorogenic acid co-administration alleviates cisplatin-induced peripheral neuropathy in rats

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology Pub Date : 2023-11-23 DOI:10.1111/fcp.12970

Çiğdem Çengelli Ünel, Ezgi Eroğlu, Orhan Özatik, Kevser Erol

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引用次数: 0

Abstract

Background

Chemotherapy-induced peripheral neuropathy (CIPN) is still an unresolved problem in cisplatin (CIS) use.

Objectives

This study investigates possible anti-neuropathic effect of chlorogenic acid (CGA) against CIS-induced CIPN in rats while also investigating the contribution of nitric oxide (NO) to this phenomenon.

Methods

Initially, CGA (250–1000 μM) was tested by MTT assay on primary DRG neurons. Subsequently, CIPN was induced in Sprague–Dawley rats by 3 mg/kg intraperitoneal injections of CIS once/week for 5 weeks. CGA (100 mg/kg) was co-administered with CIS, both alone and in combination with l-arginine (LARG) or l-nitro-arginine-methyl-ester (LNAME), to elucidate the contribution of nitrergic system to anti-neuropathic effects. Mechanical allodynia, thermal hyperalgesia, and cold plate tests were performed to test CIPN. Rotarod, footprint analysis, and activitymeter were used to evaluate motor coordination and performance. Tumor necrosis factor alpha (TNF-α) was measured as a marker of inflammation. Histological evaluations of DRG and sciatic nerves (SNs) were performed utilizing toluidine blue staining. Two-way analysis of variance and Kruskal–Wallis following Tukey's test were used as statistical analysis.

Results

Higher concentration of CGA (1000 μM) exhibited protective effect against in vitro neurotoxicity. Neither LARG nor LNAME exerted significant change in this effect. Co-administration of CGA alleviated histological abnormalities and neuropathic effects induced by CIS. Ameliorative effect of CGA was not changed in mechanical allodynia but attenuated in cold allodynia, and motor activity/coordination tests by LARG and LNAME. Neuropathic effects of CIS remained unchanged with LARG and LNAME in behavioral experiments.

Conclusion

The study identified CGA as candidate agent in mitigating CIPN. NO seems to play a modulatory role in this effect.

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绿原酸联合给药可减轻顺铂所致大鼠周围神经病变。

背景:化疗引起的周围神经病变(CIPN)仍然是顺铂(CIS)使用中未解决的问题。目的:本研究探讨绿原酸(CGA)对cis诱导大鼠CIPN可能的抗神经病变作用，同时探讨一氧化氮(NO)在这一现象中的作用。方法:采用MTT法检测CGA (250 ~ 1000 μM)对原代DRG神经元的影响。随后，Sprague-Dawley大鼠腹腔注射CIS 3 mg/kg，每周1次，连续5周诱导CIPN。CGA (100 mg/kg)与CIS联合给药，包括单独给药和与l-精氨酸(LARG)或l-硝基精氨酸甲酯(LNAME)联合给药，以阐明氮能系统在抗神经病变作用中的作用。采用机械异常性痛、热痛觉过敏和冷板试验来检测CIPN。使用旋转杆、足迹分析和活动计来评估运动协调和表现。检测肿瘤坏死因子α (TNF-α)作为炎症指标。采用甲苯胺蓝染色对DRG和坐骨神经(SNs)进行组织学评价。统计分析采用双向方差分析和Tukey检验后的Kruskal-Wallis检验。结果:较高浓度(1000 μM)的CGA对体外神经毒性具有保护作用。LARG和LNAME在这方面都没有产生显著的变化。同时给药CGA可减轻CIS引起的组织学异常和神经病变。CGA的改善作用在机械异常性痛中没有改变，但在冷异常性痛和LARG和LNAME的运动活动/协调试验中减弱。在行为实验中，CIS对LARG和LNAME的神经病变作用保持不变。结论:本研究确定CGA为缓解CIPN的候选药物。NO似乎在这一作用中起调节作用。

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.