Oxidative stress, metalloproteinase and LDH in children with intractable and non-intractable epilepsy as reflected in salivary analysis.
Oxidative stress and metalloproteinase (MMPs) may have a pivotal role in the pathogenesis of epilepsy. This study examined the underlying mechanism of epilepsy in children and especially in its intractable form, with respect to the roles of MMP's and free radicals in general and in saliva in particular. We also explored the possible diagnostic role of a compositional salivary analysis in these children, as salivary collection is simple, non-invasive (and thus 'children-friendly') and requires almost no expertise. We analyzed saliva parameters of 33 epileptic children: 22 with non-intractable (E's) and 11 with intractable epilepsy (IE's), and compared them with 16 healthy controls. Mean salivary LDH concentration in controls was 213.1±34.0IU/L, dropping by 38% (p=0.014) in E's and by 76% (p=0.0003) in IE's. Mean salivary values of peroxidase activity, SOD activity and carbonyls level were 480±14mU/mL, 1.30±0.15U/mL and 0.34±0.04nmol/mg, respectively, in controls, increasing by 6% (p=0.03), by 37% (p=0.04) and by 59% (p=0.003) in E's, and by 10% (p=0.02), by 29% (p=0.03) and by 56% (p=0.004) in IE's. Mean salivary MMP 9 concentration was 0.062±0.003 (OD) in controls, decreased by 12% (p=0.048) in E's, and by 23%, (p=0.009) in IE's. Our results enhance our understanding of epilepsy's biological underlying mechanism as reflected in the saliva of children with both intractable and non intractable disease.


CONCLUSIONS
The currently reported salivary analysis and the demonstrated salivary alterations in children suffering from epilepsy represent a novel direction. We found various salivary alterations demonstrated in the general composition as well as the oxidative and metalloproteinase analyses and more so in the intractable epilepsy group than in the non intractable epilepsy group. Hence, salivary oxidative components and MMP levels were found useful in the detection and follow-up of children with epilepsy. As such, we recommend using this non-invasive salivary analysis for diagnosis and monitoring of epileptic activity in children.
Child Neurology Unit & Epilepsy Service, Meyer Children Hospital, Rambam Health Care Campus, Haifa, Israel; Rappaport Faculty of Medicine, Technion - Israel Institute of Technology Haifa, Israel.
Eli
E
Shahar
Child Neurology Unit & Epilepsy Service, Meyer Children Hospital, Rambam Health Care Campus, Haifa, Israel.
Uri
U
Attias
Molecular Pharmacology Department and Oral Biochemistry Laboratory, Israel; Rappaport Faculty of Medicine, Technion - Israel Institute of Technology Haifa, Israel.
Dana
D
Savulescu
Child Neurology Unit & Epilepsy Service, Meyer Children Hospital, Rambam Health Care Campus, Haifa, Israel.
Jacob
J
Genizin
Molecular Pharmacology Department and Oral Biochemistry Laboratory, Israel; Rappaport Faculty of Medicine, Technion - Israel Institute of Technology Haifa, Israel. Electronic address: m.gavish@tx.technion.ac.il.
Moshe
M
Gavish
Molecular Pharmacology Department and Oral Biochemistry Laboratory, Israel; Rappaport Faculty of Medicine, Technion - Israel Institute of Technology Haifa, Israel. Electronic address: nagler@tx.technion.ac.il.
Rafael
R
Nagler
D015415:Biomarkers / Q000378:metabolism; D002648:Child; D004827:Epilepsy / Q000175:diagnosis* / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D045726:Metalloproteases / Q000032:analysis / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D012471:Salivary Proteins and Peptides / Q000378:metabolism*
D015415:Biomarkers; D012471:Salivary Proteins and Peptides; D007770:L-Lactate Dehydrogenase; D045726:Metalloproteases; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
Epilepsy; Intractable epilepsy; LDH; Metalloproteinases; Oxidative stress; Saliva