title: Nobiletin restores impaired hippocampal mitochondrial bioenergetics in hypothyroidism through activation of matrix substrate-level phosphorylation.
abstract: OBJECTIVE
  Evaluation of the effect of citrus flavonoid - nobiletin on the bioenergetics of synaptic and non-synaptic mitochondria in the hippocampus of hypothyroid rats.
  
  
  METHODS
  Male Wistar rats were divided into hypothyroid (methimazole-treated), nobiletin supplemented hypothyroid, thyroxine-treated hypothyroid, and euthyroid (control) groups. Synaptic and non-synaptic (cell) mitochondria were isolated from hippocampus. Oligomycin-sensitive, oligomycin-insensitive, α-ketoglutarate dehydrogenase-dependent synthesis of adenosine triphosphate (ATP), succinate dehydrogenase, and hexokinase activities were determined luminometrically and spectrophotometrically, respectively.
  
  
  RESULTS
  Decreased synthesis of oligomycin-sensitive and oligomycin-insensitive ATP in hypothyroid rat hippocampus was observed in synaptic and non-synaptic mitochondria. Supplementation of hypothyroid rats with nobiletin increases oligomycin-insensitive and α-ketoglutarate-dependent production of ATP in both types of mitochondria. The activity of succinate dehydrogenase in non-synaptic mitochondria and the activities of hexokinase in both types of mitochondria were normalized in nobiletin-treated hypothyroid rats.
  
  
  CONCLUSIONS
  Nobiletin restores reduced mitochondrial metabolism in hypothyroid rat hippocampus through acceleration of matrix substrate-level phosphorylation that may be important for the prevention of hypometabolic complications in neurological disorders.
authors.forename: Natia
authors.initials: N
authors.lastname: Jojua
authors.forename: Nino
authors.initials: N
authors.lastname: Sharikadze
authors.forename: Elene
authors.initials: E
authors.lastname: Zhuravliova
authors.forename: Elnari
authors.initials: E
authors.lastname: Zaalishvili
authors.forename: David G
authors.initials: DG
authors.lastname: Mikeladze
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects*; D047309:Flavones / Q000494:pharmacology*; D006593:Hexokinase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007037:Hypothyroidism / Q000188:drug therapy*; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013385:Succinate Dehydrogenase / Q000378:metabolism
chemical_list: D047309:Flavones; D000255:Adenosine Triphosphate; C008661:nobiletin; D007655:Ketoglutarate Dehydrogenase Complex; D013385:Succinate Dehydrogenase; D006593:Hexokinase
keywords: Bioenergetics; Hippocampus; Hypothyroidism; Mitochondria; Nobiletin