title: Ornithine phenylacetate prevents disturbances of motor-evoked potentials induced by intestinal blood in rats with portacaval anastomosis.
abstract: OBJECTIVE
  Ornithine phenylacetate (OP) is a new drug that has been proposed for the treatment of hepatic encephalopathy (HE) because it decreases plasma ammonia. We performed a study to assess if OP would impact on neuronal function.
  
  
  METHODS
  Motor-evoked potentials (MEP), a surrogate of hepatic encephalopathy, were assessed (without anesthesia) in rats with portacaval anastomosis (PCA) that received gastrointestinal blood (GIB). Rats were pre-treated with OP prior to GIB. Ammonia and related metabolites (plasma, urine, and brain microdialysis) were assessed by HPLC and mass spectroscopy.
  
  
  RESULTS
  OP (one dose or 3 days) prevented disturbances in MEP induced by GIB in PCA rats. In rats treated with OP for 3 days, the amplitude and latency of MEP remained stable (-1% and +1%), while in the control group the amplitude decreased -21% and the latency increased +12% (p<0.01). OP attenuated the rise of ammonia in plasma by 45%, ammonia in brain microdialysate by 48%, induced a faster glutamine rise and the appearance of phenylacetylglutamine in plasma and urine. In addition, OP was associated with a lower concentration of ammonia and glutamate in brain microdialysate (approx. 50%).
  
  
  CONCLUSIONS
  OP prevents abnormalities in MEP precipitated by GIB in a model of HE. This is probably due to the enhancement of glutamine synthesis and metabolism, which results in a lower rise of plasma ammonia and the prevention of changes in glutamate in microdialysate. Thus, OP may be a good drug to prevent HE precipitated by gastrointestinal bleeding.
authors.affiliation: Servei de Medicina Interna-Hepatologia, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Oria
authors.forename: Jordi
authors.initials: J
authors.lastname: Romero-Giménez
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Arranz
authors.forename: Encarnació
authors.initials: E
authors.lastname: Riudor
authors.forename: Núria
authors.initials: N
authors.lastname: Raguer
authors.forename: Juan
authors.initials: J
authors.lastname: Córdoba
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D019054:Evoked Potentials, Motor / Q000187:drug effects*; D005973:Glutamine / Q000031:analogs & derivatives / Q000097:blood; D006501:Hepatic Encephalopathy / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D009952:Ornithine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010648:Phenylacetates / Q000008:administration & dosage* / Q000097:blood; D011167:Portacaval Shunt, Surgical / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000596:Amino Acids; D010648:Phenylacetates; D005973:Glutamine; D000641:Ammonia; C003089:phenylacetylglutamine; C572232:ornithine phenylacetate; D009952:Ornithine; C025136:phenylacetic acid