Unknown

Dataset Information

0

Increased α-tocopherol metabolism in horses with equine neuroaxonal dystrophy.


ABSTRACT:

Background

Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM) is an inherited neurodegenerative disorder associated with a vitamin E deficiency within the first year of life. Vitamin E consists of 8 isoforms metabolized by the CYP4F2 enzyme. No antemortem diagnostic test currently exists for eNAD/EDM.

Hypothesis/objectives

Based on the association of α-tocopherol deficiency with the development of eNAD/EDM, we hypothesized that the rate of α-tocopherol, but not γ-tocopherol or tocotrienol metabolism, would be increased in eNAD/EDM-affected horses.

Animals

Vitamin E metabolism: Proof of concept (POC) study; eNAD/EDM-affected (n = 5) and control (n = 6) horses. Validation study: eNAD/EDM-affected Quarter Horses (QHs; n = 6), cervical vertebral compressive myelopathy affected (n = 6) horses and control (n = 29) horses. CYP4F2 expression and copy number: eNAD/EDM-affected (n = 12) and age- and sex-matched control (n = 11-12) horses.

Methods

The rates of α-tocopherol/tocotrienol and γ-tocopherol/tocotrienol metabolism were assessed in equine serum (POC and validation) and urine (POC only) using liquid chromatography tandem mass spectrometry (LC-MS/MS). Quantitative reverse-transcriptase PCR (qRT-PCR) and droplet digital (dd)-PCR were used to assay expression and genomic copy number of a CYP4F2 equine ortholog.

Results

Metabolic rate of α-tocopherol was increased in eNAD/EDM horses (POC,P < .0001; validation, P = .03), with no difference in the metabolic rate of γ-tocopherol. Horses with eNAD/EDM had increased expression of the CYP4F2 equine orthologue (P = .02) but no differences in copy number.

Conclusions and clinical importance

Increased α-tocopherol metabolism in eNAD/EDM-affected QHs provides novel insight into alterations in vitamin E processing in eNAD/EDM and highlights the need for high-dose supplementation to prevent the clinical phenotype in genetically susceptible horses.

SUBMITTER: Hales EN 

PROVIDER: S-EPMC8478026 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC4831564 | biostudies-literature
| S-EPMC6189351 | biostudies-literature
| S-EPMC4557866 | biostudies-literature
| S-EPMC5154892 | biostudies-literature
| S-EPMC1698558 | biostudies-literature
| S-EPMC7193406 | biostudies-literature
| S-EPMC4873246 | biostudies-literature
| S-EPMC7392694 | biostudies-literature
| S-EPMC4640708 | biostudies-literature
| S-EPMC7016928 | biostudies-literature