title: Tridecanoin is anticonvulsant, antioxidant, and improves mitochondrial function.
abstract: The hypothesis that chronic feeding of the triglycerides of octanoate (trioctanoin) and decanoate (tridecanoin) in "a regular non-ketogenic diet" is anticonvulsant was tested and possible mechanisms of actions were subsequently investigated. Chronic feeding of 35E% of calories from tridecanoin, but not trioctanoin, was reproducibly anticonvulsant in two acute CD1 mouse seizure models. The levels of beta-hydroxybutyrate in plasma and brain were not significantly increased by either treatment relative to control diet. The respective decanoate and octanoate levels are 76 µM and 33 µM in plasma and 1.17 and 2.88 nmol/g in brain. Tridecanoin treatment did not alter the maximal activities of several glycolytic enzymes, suggesting that there is no reduction in glycolysis contributing to anticonvulsant effects. In cultured astrocytes, 200 µM of octanoic and decanoic acids increased basal respiration and ATP turnover, suggesting that both medium chain fatty acids are used as fuel. Only decanoic acid increased mitochondrial proton leak which may reduce oxidative stress. In mitochondria isolated from hippocampal formations, tridecanoin increased respiration linked to ATP synthesis, indicating that mitochondrial metabolic functions are improved. In addition, tridecanoin increased the plasma antioxidant capacity and hippocampal mRNA levels of heme oxygenase 1, and FoxO1.
authors.affiliation: 1 Department of Pharmacology, School of Biomedical Sciences, The University of Queensland, St. Lucia, Australia.
authors.forename: Kah Ni
authors.initials: KN
authors.lastname: Tan
authors.affiliation: 1 Department of Pharmacology, School of Biomedical Sciences, The University of Queensland, St. Lucia, Australia.|2 Department of Nutrition, Faculty of Medicine, The University of Chile, Santiago, Chile.
authors.forename: Catalina
authors.initials: C
authors.lastname: Carrasco-Pozo
authors.affiliation: 1 Department of Pharmacology, School of Biomedical Sciences, The University of Queensland, St. Lucia, Australia.
authors.forename: Tanya S
authors.initials: TS
authors.lastname: McDonald
authors.affiliation: 3 Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Puchowicz
authors.affiliation: 1 Department of Pharmacology, School of Biomedical Sciences, The University of Queensland, St. Lucia, Australia.
authors.forename: Karin
authors.initials: K
authors.lastname: Borges
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D003651:Decanoates / Q000097:blood; D004195:Disease Models, Animal; D008297:Male; D008815:Mice, Inbred Strains; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D012640:Seizures / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D014280:Triglycerides / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D000975:Antioxidants; D001786:Blood Glucose; D003651:Decanoates; D014280:Triglycerides; C559070:tridecanoin; D020155:3-Hydroxybutyric Acid
keywords: Antioxidant; anti-seizure; decanoate; mitochondrial function; octanoate