驱虫药和抗生素治疗解决实验性滴虫病的肠道炎症浸润。

IF 3.8 2区 医学 Q2 CHEMISTRY, MEDICINAL
Tathiane de Oliveira Alves Costa, Dayane Alvarinho de Oliveira, Alessandra Campos da Silva, Eduardo José Lopes-Torres
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引用次数: 0

摘要

尽管在人类健康方面取得了重大进展,但土壤传播蠕虫(STH)继续构成重大的公共卫生挑战,特别是在贫困地区。阿苯达唑用于治疗STH已有40多年的历史,目前仍广泛应用于大规模药物管理项目。然而,据估计,全球仍有超过15亿人受到感染,巴西报告的人类鞭虫病患病率为5.41%。由于毛滴虫对上皮粘膜的影响,包括组织损伤、生态失调、细菌易位、炎症浸润、肠层肥大等,因此被广泛应用于小鼠模型研究毛滴虫病。这些影响有助于高寄生虫负荷感染的更严重后果,如直肠脱垂。目前,肠道蠕虫与细菌之间的相互作用的研究仍然有限,尽管它可能对病理协同作用有贡献。传统的STH治疗方法的耐药性日益受到关注,这突出表明需要新的治疗方法。本研究旨在评价驱虫药阿苯达唑与抗生素哌拉西林钠加他唑巴坦联合使用对慢性实验性滴虫病炎症过程的影响。瑞士韦伯斯特小鼠感染了150个胚胎鼠耳绦虫卵。35 d后,将小鼠分为4组:1组(抗生素治疗)、2组(驱虫药治疗)、3组(联合治疗)、4组(对照组,不治疗)。治疗后,对小鼠实施安乐死,并进行不同的分析。结果显示,与接受治疗的小鼠相比,未经治疗的小鼠的腹膜巨噬细胞数量显著增加。与未经治疗的感染小鼠不同,抗生素治疗的小鼠在上皮粘膜下层没有显示入侵细菌。与仅使用抗生素的组相比,接受驱虫药治疗的组显示出更多的死虫。此外,驱虫药和抗生素联合治疗显示出对线虫定植和细菌易位的更有效控制,潜在地减少了感染的继发影响,如细菌易位和相关的炎症过程。这些发现表明,我们的结果可以为开发新的治疗方案铺平道路,将驱虫药和抗生素治疗结合起来。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Anthelmintic and Antibiotic Therapy Resolves Intestinal Inflammatory Infiltration in Experimental Trichuriasis.

Despite significant advances in human health, soil-transmitted helminths (STH) continue to pose a major public health challenge, particularly in impoverished regions. Albendazole has been used to treat STH for over 40 years and remains widely utilized in mass drug administration programs. However, it is estimated that over 1.5 billion people are still infected globally, with Brazil reporting a prevalence of 5.41% for human trichuriasis. The nematode Trichuris muris is widely used in murine models to study trichuriasis due to its impact on the epithelial mucosa, including tissue damage, dysbiosis, bacterial translocation, inflammatory infiltrate, and intestinal layer hypertrophy. These effects contribute to the more severe consequence of high parasite load infections, such as rectal prolapse. Currently, research on the interaction between intestinal helminths and bacteria remains limited, despite its potential contribution to pathological synergy. Drug resistance in conventional STH treatments is a growing concern, highlighting the need for new therapeutic approaches. This study aimed to evaluate the impact of combining the anthelmintic albendazole with the antibiotics piperacillin sodium plus tazobactam on the inflammatory process during chronic experimental trichuriasis. Swiss Webster mice were infected with 150 embryonated T. muris eggs. After 35 days, the mice were divided into four groups: Group 1 (antibiotic treatment), Group 2 (anthelmintic treatment), Group 3 (combined treatment), and Group 4 (control, no treatment). After treatments, the mice were euthanized, and different analyses were conducted. Results showed that untreated mice had a significantly higher number of peritoneal macrophages compared to those that received treatment. Antibiotic-treated mice did not show invading bacteria in the epithelial submucosa, unlike untreated infected mice. The groups that received anthelmintic treatment exhibited a higher number of dead worms compared to the antibiotic-only group. Additionally, the combination of anthelmintic and antibiotic treatments demonstrated more effective control of nematode colonization and bacterial translocation, potentially reducing the secondary impacts of the infection, such as bacterial translocation and the associated inflammatory processes. These findings suggest that our results could pave the way for the development of new treatment protocols for STH, integrating both anthelmintic and antibiotic therapies.

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来源期刊
ACS Infectious Diseases
ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES
CiteScore
9.70
自引率
3.80%
发文量
213
期刊介绍: ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.
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