Dataset Information

Plasma metabolome reveals altered oxidative stress, inflammation, and amino acid metabolism in dogs with idiopathic epilepsy.

ABSTRACT:

OBJECTIVE: Idiopathic epilepsy (IE) is the most common chronic neurological disease in dogs, and an established natural animal model for human epilepsy types with genetic and unknown etiology. However, the metabolic pathways underlying IE remain largely unknown. METHODS: Plasma samples of healthy dogs (n = 39) and dogs with IE (n = 49) were metabolically profiled (n = 121 known target metabolites) and fingerprinted (n = 1825 untargeted features) using liquid chromatography coupled to mass spectrometry. Dogs with IE were classified as drug-sensitive (DS) (n = 22) or drug-resistant (DR) (n = 27). All dogs received the same standard adult maintenance diet for minimum 20 days (35 ± 11 days) before sampling. Data were analysed using a combination of univariate (one-way ANOVA or Kruskal-Wallis rank sum test), multivariate (limma, OPLS-DA) and pathway enrichment statistical analysis. RESULTS: In dogs with both DR and DS IE, a distinct plasma metabolic profile and fingerprint compared to healthy dogs was observed. Metabolic pathways involved in these alterations included oxidative stress, inflammation and amino acid metabolism. Vitamin B6 was found to play a key role, with significantly lower plasma concentrations found in DS (P = 0.001) and DR (P = 0.005) compared to healthy dogs. SIGNIFICANCE: Our data provide new insights in the metabolic pathways underlying IE in dogs, further substantiating its potential as a sentinel for humans with epilepsy, reflected by related metabolic changes in oxidative stress metabolites and vitamin B6. Even more, several metabolites within the uncovered pathways offer promising therapeutic targets for the management of IE, primarily for dogs, and ultimately for humans.

INSTRUMENT(S): Liquid Chromatography MS - alternating - reverse phase

PROVIDER: MTBLS10915 | MetaboLights | 2025-07-02

REPOSITORIES: MetaboLights

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 325

Publications

Plasma metabolome reveals altered oxidative stress, inflammation, and amino acid metabolism in dogs with idiopathic epilepsy.

Verdoodt Fien F Bhatti Sofie F M SFM Molina Jenifer J Van Ham Luc L Vanhaecke Lynn L Junius Greet G Hemeryck Lieselot Y LY Hesta Myriam M

Epilepsia 20250113 4

<h4>Objective</h4>Idiopathic epilepsy (IE) is the most common chronic neurological disease in dogs and an established natural animal model for human epilepsy types with genetic and unknown etiology. However, the metabolic pathways underlying IE remain largely unknown.<h4>Methods</h4>Plasma samples of healthy dogs (n = 39) and dogs with IE (n = 49) were metabolically profiled (n = 121 known target metabolites) and fingerprinted (n = 1825 untargeted features) using liquid chromatography coupled to ...[more]

PMID: 39804158

Similar Datasets

Project description:Introduction: The relationship between epilepsy and cognitive dysfunction has been investigated in canines, and memory impairment was prevalent in dogs with epilepsy. There is some evidence that canines with epilepsy have greater amyloid-β (Aβ) accumulation and neuronal degeneration than healthy controls. The present study investigated plasma Aβ42 levels and performed proteomic profiling in dogs with refractory epilepsy and healthy dogs. Methods: In total, eight dogs, including four healthy dogs and four dogs with epilepsy, were included in the study. Blood samples were collected to analyze Aβ42 levels and perform proteomic profiling. Changes in the plasma proteomic profiles of dogs were determined by nano LC-MS/MS. Results and discussion: The plasma Aβ42 level was significantly higher in dogs with epilepsy (99 pg/mL) than in healthy dogs (5.9 pg/mL). In total, 155 proteins were identified, and of these, the expression of 40 proteins was altered in epilepsy. Among these proteins, which are linked to neurodegenerative diseases, 10 (25%) were downregulated in dogs with epilepsy, whereas 12 (30%) were upregulated. The expression of the acute phase proteins haptoglobin and α2-macroglobulin significantly differed between the groups. Complement factor H and ceruloplasmin were only detected in epilepsy dogs, suggesting that neuroinflammation plays a role in epileptic seizures. Gelsolin, which is involved in cellular processes and cytoskeletal organization, was only detected in healthy dogs. Gene Ontology annotation revealed that epilepsy can potentially interfere with biological processes, including cellular processes, localization, and responses to stimuli. Seizures compromised key molecular functions, including catalytic activity, molecular function regulation, and binding. Defense/immunity proteins were most significantly modified during the development of epilepsy. In Kyoto Encyclopedia of Genes and Genomes pathway analysis, complement and coagulation cascades were the most relevant signaling pathways affected by seizures. The findings suggested that haptoglobin, ceruloplasmin, α2-macroglobulin, complement factor H, and gelsolin play roles in canine epilepsy and Aβ levels based on proteomic profiling. These proteins could represent diagnostic biomarkers that, after clinical validation, could be used in veterinary practice as well as proteins relevant to disease response pathways. To determine the precise mechanisms underlying these relationships and their implications in canine epilepsy, additional research is required.

Project description:Chagas disease causes a cardiac illness characterized by immunoinflammatory reactions leading to myocardial fibrosis and remodeling. The development of Chronic Chagas Cardiomyopathy (CCC) in some patients while others remain asymptomatic is not fully understood, but dysregulated inflammatory responses are implicated. The Aryl hydrocarbon receptor (AhR) plays a crucial role in regulating inflammation. Certain tryptophan (Trp) metabolites have been identified as AhR ligands with regulatory functions. We investigated AhR expression, agonist response, ligand production, and AhR-dependent responses, such as IDO activation and regulatory T (Treg) cells induction, in two T.cruzi-infected mouse strains (B6 and Balb/c) showing different polymorphisms in AhR. Furthermore, we assessed the metabolic profile of Trp catabolites and AhR agonistic activity levels in plasma samples from patients with chronic Chagas disease (CCD) and healthy donors (HD) using a luciferase reporter assay and liquid chromatography-mass spectrophotometry (LC-MS) analysis. T. cruzi-infected B6 mice showed impaired AhR-dependent responses compared to Balb/c mice, including reduced IDO activity, kynurenine levels, Treg cell induction, CYP1A1 up-regulation, and AhR expression following agonist activation. Additionally, B6 mice exhibited no detectable 34 AhR agonist activity in plasma and displayed lower CYP1A1 up-regulation and AhR expression upon agonist activation. Similarly, CCC patients had decreased AhR agonistic activity in plasma compared to HD patients and exhibited dysregulation in Trp metabolic pathways, resulting in altered plasma metabolite profiles. Notably, patients with severe CCC specifically showed increased N-acetylserotonin levels in their plasma. The methods and findings presented here contribute to a better understanding of CCC development mechanisms and may identify potential specific biomarkers for T. cruzi infection and the severity of associated heart disease. These insights could be valuable in designing new therapeutic strategies. Ultimately, this research aims to establish the AhR agonistic activity and Trp metabolic profile in plasma as an innovative, non-invasive predictor of prognosis for chronic Chagas disease.

			Action	DRS
	230308_sf001.raw	Raw
	230308_sf002_STD1.raw	Raw
	230308_sf003_STD1.raw	Raw
	230308_sf004_STD2.raw	Raw
	230308_sf005_STD3.raw	Raw

Dataset Information

Plasma metabolome reveals altered oxidative stress, inflammation, and amino acid metabolism in dogs with idiopathic epilepsy.

Dataset's files

Publications

Plasma metabolome reveals altered oxidative stress, inflammation, and amino acid metabolism in dogs with idiopathic epilepsy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets