Impact of Visceral Leishmaniasis on Local Organ Metabolism in Hamsters.

Impact of Visceral Leishmaniasis on Local Organ Metabolism in Hamsters.
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DOI:
10.3390/metabo12090802
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发表时间:
2022-08-27
期刊:
影响因子:
4.1
通讯作者:
--
中科院分区:
生物学3区
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--
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利什曼原虫(Leishmania)是一种细胞内寄生虫,对人类具有不同的物种致病性,并引起利什曼病疾病。 Leishmania Donovani引起内脏利什曼病(VL),表现为肝肾上腺肿,发烧,全血细胞减少症和高gammagamaglobloblobloblobloinemia。如果没有治疗,VL可能会导致死亡,尤其是在免疫功能低下的人中。当前的治疗通常会产生重大的不利影响,并且在某些国家报告了抵抗。确定在VL期间扰动的代谢产物可能会导致我们找到针对疾病发病机理的新疗法。因此,我们比较了跨器官(脾脏,肝脏和肠道)的Donovani感染和未感染的仓鼠之间的代谢扰动。提取代谢物,通过液相色谱 - 质谱法分析,并用Mzmine和Molecular网络处理以注释代谢物。我们发现,在所有三个部位,包括甘油磷脂,神经酰胺,酰基肉碱,肽,肽,嘌呤和氨基酸在内的所有三个部位通常受到感染的影响很少。根据VL症状和寄生虫的偏向主义,与脾和肠道,肝脏,肝脏和肠道相比,脾脏和肝脏之间的扰动代谢产物的重叠更大。针对与这些代谢产物家庭相关的途径将是下一个重点,它可以导致我们为VL找到更有效的治疗方法。
Leishmania is an intracellular parasite with different species pathogenic to humans and causing the disease leishmaniasis. Leishmania donovani causes visceral leishmaniasis (VL) that manifests as hepatosplenomegaly, fever, pancytopenia and hypergammaglobulinemia. If left without treatment, VL can cause death, especially in immunocompromised people. Current treatments have often significant adverse effects, and resistance has been reported in some countries. Determining the metabolites perturbed during VL can lead us to find new treatments targeting disease pathogenesis. We therefore compared metabolic perturbation between L. donovani-infected and uninfected hamsters across organs (spleen, liver, and gut). Metabolites were extracted, analyzed by liquid chromatography-mass spectrometry, and processed with MZmine and molecular networking to annotate metabolites. We found few metabolites commonly impacted by infection across all three sites, including glycerophospholipids, ceramides, acylcarnitines, peptides, purines and amino acids. In accordance with VL symptoms and parasite tropism, we found a greater overlap of perturbed metabolites between spleen and liver compared to spleen and gut, or liver and gut. Targeting pathways related to these metabolite families would be the next focus that can lead us to find more effective treatments for VL.
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