Lipid peroxidation biomarkers for evaluating oxidative stress in equine neuroaxonal dystrophy

Abstract

BackgroundEquine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM) is a neurodegenerative disorder affecting genetically predisposed foals maintained on an α‐tocopherol (α‐TOH) deficient diet. Currently no antemortem diagnostic test for eNAD/EDM is available.HypothesisBecause α‐TOH deficiency is associated with increased lipid peroxidation, it was hypothesized that F2‐isoprostanes (F2IsoP), F4‐neuroprostanes (F4NP) and oxysterols derived from free radical oxidation would be increased in the cerebrospinal fluid (CSF) and neural tissue of eNAD/EDM affected horses and could serve as potential biomarkers for disease.AnimalsIsoprostane Study A: 14 Quarter horse foals (10 healthy foals and 4 eNAD/EDM affected foals) at 1 and 6 months of age. Isoprostane Study B: 17 eNAD/EDM affected and 10 unaffected horses ≥ 1‐4 years of age. Oxysterol study: eNAD/EDM affected (n = 14, serum; n = 11, CSF; n = 10, spinal cord [SC]) and unaffected horses 1‐4 years of age (n = 12, serum; n = 10, CSF; n = 7, SC).ProceduresCerebrospinal fluid [F2IsoP] and [F4NP] were assessed using gas chromatography‐negative ion chemical ionization mass spectrometry. Serum, CSF, and cervical SC [oxysterols] were quantified using high performance liquid chromatography mass spectrometry. Results were compared with respective α‐TOH concentrations.ResultsSpinal cord [7‐ketocholesterol], [7‐hydroxycholesterol], and [7‐keto‐27‐hydrocholesterol] were higher in eNAD/EDM horses whereas [24‐ketocholesterol] was lower. No significant difference was found in CSF [F2IsoP] and [F4NP], serum [oxysterols] and CSF [oxysterols] between eNAD/EDM affected and unaffected horses. No correlation was found between [F2IsoP], [F4NP], or [oxysterols] and respective [α‐TOH].Conclusions and Clinical ImportanceIn the SC, targeted markers of cholesterol oxidation were significantly increased in horses with eNAD/EDM.

Biomarkers in Stress Related Diseases/Disorders: Diagnostic, Prognostic, and Therapeutic Values

“…These are prostaglandin-like compounds released from the peroxidation of arachidonic acid, independently of the normal cyclo-oxygenase pathway, which are subsequently released for circulation by phospholipases (Griffiths and Moller, 2002; Stafforini et al, 2006; Czerska et al, 2016). The presence of isoprostanes, especially F2-isoprostane (F2-Isops), can be quantified from various biological sources, such as blood (Siti Hajar et al, 2018), urine (Roy et al, 2015), cerebrospinal fluid (Finno et al, 2018), or other fluids or tissues (Annelies et al, 2018; Finno et al, 2018; Jadoon and Malik, 2018). F2-Isops, being the most stable among the isoprostanes, is the most potent isoprostane biomarker and its level can reflect the oxidative status of vital organs, such as liver or kidneys (Morrow, 2005; Musiek et al, 2005).…”

“…Interestingly, it is reported that long-term supplementation with vitamin E reduces oxidative stress in smokers, which is determined by 8-iso-PGF2α detection (Guertin et al, 2016). Isoprostanes have been evaluated as biomarkers in equine neuroaxonal dystrophy (Finno et al, 2018), Creutzfeldt-Jakob disease, Huntington's disease, Alzheimer's disease, multiple sclerosis (Jadoon and Malik, 2018), Attention-Deficit/Hyperactivity Disorder (ADHD) (Annelies et al, 2018), and in passive smokers (Siti Hajar et al, 2018).…”

The Implication of Reactive Oxygen Species and Antioxidants in Knee Osteoarthritis

“…Isoprostanes (IsoPs) are generated by the peroxidation of polyunsaturated fatty acids. The species F2-IsoPs are the most common, derived from arachidonic acid [ 134 ], and can be used as a mediator of oxidative stress or a nonenzymatic biomarker of endogenous lipid peroxidation [ 135 , 136 ]. Elevated concentrations of IsoPs were detected in serum, synovial fluid, and synovial membrane biopsy in patients with KOA or meniscal and cruciate ligament lesions [ 137 ].…”

“…Elevated concentrations of IsoPs were detected in serum, synovial fluid, and synovial membrane biopsy in patients with KOA or meniscal and cruciate ligament lesions [ 137 ]. The determinations could be performed from plasma, saliva [ 138 ], cerebrospinal fluid samples [ 136 ], or various tissue types, by gas chromatography-mass spectrometry (GC-MS) methods [ 138 ]. Decreased F2-IsoPs levels are associated with vitamin C administration [ 139 ] and with the consumption of antioxidant-rich fruits [ 140 ].…”

Equine degenerative myeloencephalopathy: prevalence, impact, and management

“…It is known that d -α-tocopherol (RRR-α-tocopherol) is the most potent, bioavailable isoform of vitE, 23 and that oxidative stress is occurring in the brainstem and spinal cord of eNAD/EDM affected horses. 4 , 35 Current research is ongoing to determine the exact cause of this oxidative injury and how vitE prevents such damage.…”