Changes in metabolomic profile in dogs with hepatic encephalopathy secondary to congenital portosystemic shunt suggests mitochondrial homeostasis disturbances.

IF 1.6 3区 农林科学 Q2 VETERINARY SCIENCES
Ana Fernandez Gallego, Jair Marques, Dominic Kurian, Federico Diez, Richard J Mellanby, Adam G Gow, Alexander von Kriegsheim, Kiterie M E Faller
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引用次数: 0

Abstract

Objective: To identify specific metabolomic changes in dogs showing signs of hepatic encephalopathy (HE) compared to those not showing obvious neurological signs and to follow these changes following medical treatment.

Methods: In this prospective observational study, we recruited 10 client-owned dogs diagnosed with congenital portosystemic shunt (from March 2021 through October 2022). The sera of dogs with or without signs of HE at the time of diagnosis of congenital portosystemic shunt and following medical treatment for more than 4 weeks were analyzed by UPLC-MS.

Results: Dogs showing signs of HE at the time of diagnosis (n = 6) had significantly lower serum concentrations of taurine (fold change [FC], 0.44), creatine (FC, 0.32), and guanine (FC, 0.45) and higher serum concentrations of 3-hydroxybenzaldehyde (FC, 2.51) than their counterparts not showing signs of HE (4). A marked albeit nonsignificant decrease in serum stearate concentrations was also observed in the HE group (FC, 0.12). Following medical treatment, which improved neurological signs, the concentrations of these metabolites, particularly taurine, normalized to concentrations similar to the non-HE group.

Conclusions: Dogs with HE exhibit a different serum metabolomic profile compared to dogs without signs of HE. The main changes are suggesting disturbances in mitochondrial homeostasis in dogs suffering from HE.

Clinical relevance: Supporting mitochondrial function could form the basis of new therapeutic strategies in HE and merits further investigations in future studies.

先天性门系统分流继发肝性脑病犬的代谢组学变化提示线粒体稳态紊乱。
目的:确定肝性脑病(HE)症状犬与未表现明显神经症状犬的特定代谢组学变化,并在药物治疗后跟踪这些变化。方法:在这项前瞻性观察研究中,我们招募了10只诊断为先天性门静脉系统分流的客户犬(从2021年3月到2022年10月)。采用UPLC-MS对诊断为先天性门系统分流及治疗4周以上的HE症状犬的血清进行分析。结果:诊断时出现HE症状的狗(n = 6)血清牛磺酸(fold change [FC], 0.44)、肌酸(fold change [FC], 0.32)和鸟嘌呤(fold change [FC], 0.45)浓度显著低于未出现HE症状的狗(n = 6),血清3-羟基苯甲醛(3-hydroxybenzaldehyde, FC, 2.51)浓度显著高于未出现HE症状的狗(4)。在HE组中,血清硬脂酸盐浓度也显著下降(FC, 0.12)。经过药物治疗,神经系统症状得到改善,这些代谢物的浓度,特别是牛磺酸,正常化到与非he组相似的浓度。结论:与没有HE症状的狗相比,HE狗表现出不同的血清代谢组学特征。主要的变化表明,患有HE的狗的线粒体稳态受到干扰。临床意义:支持线粒体功能可以形成新的治疗策略的基础,值得在未来的研究中进一步研究。
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来源期刊
CiteScore
1.70
自引率
10.00%
发文量
186
审稿时长
3 months
期刊介绍: The American Journal of Veterinary Research supports the collaborative exchange of information between researchers and clinicians by publishing novel research findings that bridge the gulf between basic research and clinical practice or that help to translate laboratory research and preclinical studies to the development of clinical trials and clinical practice. The journal welcomes submission of high-quality original studies and review articles in a wide range of scientific fields, including anatomy, anesthesiology, animal welfare, behavior, epidemiology, genetics, heredity, infectious disease, molecular biology, oncology, pharmacology, pathogenic mechanisms, physiology, surgery, theriogenology, toxicology, and vaccinology. Species of interest include production animals, companion animals, equids, exotic animals, birds, reptiles, and wild and marine animals. Reports of laboratory animal studies and studies involving the use of animals as experimental models of human diseases are considered only when the study results are of demonstrable benefit to the species used in the research or to another species of veterinary interest. Other fields of interest or animals species are not necessarily excluded from consideration, but such reports must focus on novel research findings. Submitted papers must make an original and substantial contribution to the veterinary medicine knowledge base; preliminary studies are not appropriate.
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