Examinations of the antioxidative properties of the topically administered drug bufexamac reveal new insights into its mechanism of action

Author:

Trommer Hagen1,Plätzer Manuela1,Raith Klaus1,Wohlrab Wolfgang2,Podhaisky Hans-Peter2,Neubert Reinhard H H1

Affiliation:

1. Martin-Luther-University Halle-Wittenberg, School of Pharmacy, Institute of Pharmaceutics and Biopharmaceutics, Wolfgang-Langenbeck-Straβe 4, D-06120 Halle (Saale), Germany

2. Martin-Luther-University Halle-Wittenberg, Department of Dermatology, Ernst-Kromeyer-Straβe 5–8, D-06097 Halle (Saale), Germany

Abstract

Abstract The effect of bufexamac on UV-irradiation-induced lipid peroxidation was investigated. Linolenic acid was used as a model lipid. Bufexamac was shown to be capable of reducing the amount of lipid peroxidation. The quantification was carried out by the thiobarbituric acid assay. Irradiation experiments were also performed using HaCaT keratinocytes as a model system. The oxidative changes were quantified by DNA synthesis measurements and cell viability determinations. Bufexamac was found to act antioxidatively again. To investigate free radical involvement, electron paramagnetic resonance studies were carried out. The influence of bufexamac on the concentration of hydroxyl radicals generated by the Fenton system was examined using the spin trapping technique. Moreover, the hydroxamic acid's ability to react with stable radicals was checked. The quantification assay of 2,2-diphenyl-1-picrylhydrazyl hydrate showed no concentration changes of the stable radical caused by bufexamac. In the Fenton assay antioxidative effects were measured after the addition of the drug. The qualitative changes after irradiating bufexamac were studied at a molecular level by electrospray mass spectrometry. Multiple-stage mass spectrometry experiments enabled the establishment of fragmentation schemes. Phenolic degradation products were detected. The results suggest a new interpretation of the controversially debated mechanism of action of bufexamac and indicate possible reasons for its eczema provoking potential.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

Reference27 articles.

1. Schwere Epikutantestreaktion auf Bufexamac in einem Hämorrhoidal-Therapeutikum;Bauer;Dtsch. Med. Wochenschr.,1999

2. Nichtsteroidale antiinflammatorische Substanzen;Baumgartner,1992

3. Elimination of 4-n-butoxyphenylacethydroxamic acid (bufexamac) in man;Boreham;J. Pharm. Sci.,1972

4. Microsomal lipid peroxidation;Buege;Methods Enzymol.,1978

5. Kutane Nebenwirkungen nichtsteroidaler Antiphlogistika (NSAID);Gebhardt;Z. Rheumatol.,1995

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3