Vinpocetine increases the microsporicidal effect of albendazole on Encephalitozoon intestinalis.

IF 2.7 3区 医学 Q3 INFECTIOUS DISEASES Medical mycology Pub Date : 2024-08-02 DOI:10.1093/mmy/myae072
Gülay Sezer, Ülfet Çetinkaya
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Abstract

Microsporidia are obligate, intracellular, spore-forming eukaryotic fungi that infect humans and animals. In the treatment of disseminated microsporidiosis albendazole is the choice of drug. In recent years, antiparasitic activity of phosphodiesterase (PDE) enzyme inhibitors has been demonstrated against parasites and fungi, however, there is no information on microsporidia. Vinpocetine is currently used as a cerebral vasodilator drug and also as a dietary supplement to improve cognitive functions. Vinpocetine inhibits PDE1, so we aimed to investigate whether vinpocetine alone or in combination with albendazole has any effect on the spore load of Encephalitozoon intestinalis (E. intestinalis)-infected HEK293 cells. After determining the noncytotoxic concentrations of vinpocetine and albendazole on the host cell by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, HEK293 cells were infected with E. intestinalis spores. Then, two different concentrations of vinpocetine, albendazole, and a combination of both drugs were applied to the cells with an interval of 72 h for 15 days. Spore load of the cells was analyzed by real-time PCR. After the last treatment, spore Deoxyribonucleic Acid (DNA) load was significantly reduced only in the group treated with 14 ng/ml albendazole. It was not different from control in groups treated with 7 ng/ml albendazole and 4-20 µM vinpocetine. However, the combination of vinpocetine significantly increased the effect of albendazole at both concentrations. To our knowledge, this is the first study to investigate the microsporicidal activity of vinpocetine as well as its combinations with albendazole. However, further studies are needed to investigate the mechanism of action and also confirm in vivo conditions.

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长春西汀可增强阿苯达唑对肠道头癣菌的微孢子杀灭作用。
小孢子虫是一种细胞内孢子形成的真核真菌,可感染人类和动物。阿苯达唑是治疗播散性小孢子虫病的首选药物。近年来,磷酸二酯酶(PDE)抑制剂对副寄生虫和真菌的抗寄生虫活性已得到证实,但还没有关于微孢子虫的资料。长春西汀目前被用作脑血管扩张药物和改善认知功能的膳食补充剂。长春西汀可抑制 PDE1,因此我们的目的是研究长春西汀单独使用或与阿苯达唑联合使用是否会对感染 HEK293 细胞的肠道脑线虫(E. intestinalis)的孢子量产生影响。在通过 MTT 试验确定了乙琥胺和阿苯达唑对宿主细胞的无毒浓度后,用肠孢子感染 HEK293 细胞。然后,将两种不同浓度的长春西汀、阿苯达唑以及两种药物的复方应用于细胞,间隔 72 小时,持续 15 天。通过实时荧光定量PCR分析细胞中的孢子量。在最后一次处理后,只有使用 14 毫微克/毫升阿苯达唑处理的组的孢子 DNA 量明显减少。使用 7 ng/mL 阿苯达唑和 4 - 20 µM 乙烯吡啶处理的组与对照组相比没有差异。然而,在两种浓度的阿苯达唑中,联合使用醋波西汀都能显著提高阿苯达唑的效果。据我们所知,这是首次研究乙烯泊西汀及其与阿苯达唑的组合的杀微孢子活性。不过,还需要进一步研究其作用机制,并在体内条件下进行确认。
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来源期刊
Medical mycology
Medical mycology 医学-兽医学
CiteScore
5.70
自引率
3.40%
发文量
632
审稿时长
12 months
期刊介绍: Medical Mycology is a peer-reviewed international journal that focuses on original and innovative basic and applied studies, as well as learned reviews on all aspects of medical, veterinary and environmental mycology as related to disease. The objective is to present the highest quality scientific reports from throughout the world on divergent topics. These topics include the phylogeny of fungal pathogens, epidemiology and public health mycology themes, new approaches in the diagnosis and treatment of mycoses including clinical trials and guidelines, pharmacology and antifungal susceptibilities, changes in taxonomy, description of new or unusual fungi associated with human or animal disease, immunology of fungal infections, vaccinology for prevention of fungal infections, pathogenesis and virulence, and the molecular biology of pathogenic fungi in vitro and in vivo, including genomics, transcriptomics, metabolomics, and proteomics. Case reports are no longer accepted. In addition, studies of natural products showing inhibitory activity against pathogenic fungi are not accepted without chemical characterization and identification of the compounds responsible for the inhibitory activity.
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