伊维菌素或莫西菌素单独或联合多西环素体外治疗12小时成人免疫Dirofilaria isitis的转运体基因表达和沃尔巴克氏体定量

IF 1.4 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Chiara Bazzocchi , Marco Genchi , Chiara Lucchetti , Alessandra Cafiso , Lavinia Ciuca , John McCall , Laura Helen Kramer , Alice Vismarra
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引用次数: 0

摘要

由于其显著的杀幼虫活性,大环内酯(MLs)被用于预防犬心丝虫病(免疫双丝虫炎)。它们也被证明在长期服用后可以消灭成体寄生虫,具有所谓的“慢杀”效果。此外,最近的研究表明,与单独使用MLs相比,强力霉素和MLs联合使用可以消除内共生沃尔巴克氏菌,具有更好的杀虫效果。据推测,强力霉素/MLs之间的明显协同作用可能是由于与药物外排转运蛋白的相互作用。本研究的目的是评估几种运输蛋白的基因表达,在体外分别用多西环素、伊维菌素、莫西丁素或伊维菌素或莫西丁素与多西环素联合治疗12小时的成年免疫缺陷杆菌。定量PCR分析显示对治疗有性别依赖的反应。在雌性蠕虫中,与单独使用强力霉素和与伊维菌素联合使用时相比,dim - ppp -10、dim - half -1和dim - half -5上调。莫西丁未引起基因表达的变化。在雄性中,莫西菌素单独给药可诱导Dim-pgp-10、dim -pgp-11和Di-avr-14轻微升高,而伊维菌素联合多西环素可显著上调ML受体Di-avr-14。这些结果表明,两类药物之间可能存在协同作用,男性与女性对杀虫效应的不同易感性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Transporter gene expression and Wolbachia quantification in adults of Dirofilaria immitis treated in vitro with ivermectin or moxidectin alone or in combination with doxycycline for 12 h

Due to their marked larvicidal activity, macrocyclic lactones (MLs) are used for the prevention of heartworm disease ( Dirofilaria immitis) in dogs. They have also been shown to eliminate adult parasites after long-term administration, with a so-called “slow-kill” effect. In addition, recent studies have established that a combination of doxycycline, which eliminates the endosymbiont Wolbachia, and MLs has superior adulticide effects when compared to MLs alone. It has been hypothesized that the apparent synergism between doxycycline/MLs may be due to interaction with drug efflux transport proteins. The aim of the present study was to evaluate gene expression of several transport proteins in D. immitis adults treated in vitro either with doxycycline alone, ivermectin alone, moxidectin alone, or a combination of ivermectin or moxidectin with doxycycline for 12 h. Quantitative PCR analysis showed a sex-dependent response to treatments. In female worms, Dim-pgp-10, Dim-haf-1 and Dim-haf-5 were upregulated compared to controls with doxycycline alone and when combined with ivermectin. Moxidectin did not induce any changes in gene expression. In males, moxidectin administered alone induced a slight increase in Dim-pgp-10, Dim-pgp-11and Di-avr-14, while ivermectin in combination with doxycycline produced significant upregulation of the ML receptor Di-avr-14. These results suggest possible synergism between the two drug classes and different susceptibility of males vs. females to adulticide effects.

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来源期刊
CiteScore
2.90
自引率
0.00%
发文量
51
审稿时长
63 days
期刊介绍: The journal provides a medium for rapid publication of investigations of the molecular biology and biochemistry of parasitic protozoa and helminths and their interactions with both the definitive and intermediate host. The main subject areas covered are: • the structure, biosynthesis, degradation, properties and function of DNA, RNA, proteins, lipids, carbohydrates and small molecular-weight substances • intermediary metabolism and bioenergetics • drug target characterization and the mode of action of antiparasitic drugs • molecular and biochemical aspects of membrane structure and function • host-parasite relationships that focus on the parasite, particularly as related to specific parasite molecules. • analysis of genes and genome structure, function and expression • analysis of variation in parasite populations relevant to genetic exchange, pathogenesis, drug and vaccine target characterization, and drug resistance. • parasite protein trafficking, organelle biogenesis, and cellular structure especially with reference to the roles of specific molecules • parasite programmed cell death, development, and cell division at the molecular level.
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