title: Peripheral and splanchnic indole and oxindole levels in cirrhotic patients: a study on the pathophysiology of hepatic encephalopathy.
abstract: OBJECTIVE
  Intestinal bacteria metabolize tryptophan into indole, which is then further metabolized into oxindole, a sedative compound putatively involved in the pathophysiology of hepatic encephalopathy (HE). The aim of this study was to measure indole and oxindole levels in patients with cirrhosis with or without HE and to establish whether an intestinal production and a hepatic metabolism of these substances exist.
  
  
  METHODS
  We studied 10 healthy subjects (controls) and 51 cirrhotic patients: 17 without HE, 14 with a minimal HE, 8 with overt HE, and 12 who had undergone a transjugular intrahepatic portosystemic shunt (TIPS) procedure. In the last group, blood was collected from the artery, and the portal and hepatic veins during TIPS construction and from the peripheral veins before, immediately after, and at weekly intervals during the first month after TIPS.
  
  
  RESULTS
  Plasma indole levels were significantly higher in patients with overt HE. Oxindole levels were higher in cirrhotics than in controls. Indole and ammonia were significantly correlated (r=0.66). Peripheral and splanchnic determinations showed that indole was produced in the intestine and cleared by the liver, similar to ammonia. TIPS implantation increased both indole and ammonia levels. After TIPS, the psychometric performance worsened in 4 of the 12 patients. The increase in indole plasma concentrations in these four patients was higher than in those who remained stable after undergoing TIPS.
  
  
  CONCLUSIONS
  Indole correlates with HE and has a significant intestinal production and hepatic extraction; its level increases after TIPS and is related to psychometric performance. These data suggest that indole may be involved in the pathophysiology of HE.
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy. oliviero.riggio@uniroma1.it
authors.forename: Oliviero
authors.initials: O
authors.lastname: Riggio
authors.forename: Guido
authors.initials: G
authors.lastname: Mannaioni
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Ridola
authors.forename: Stefania
authors.initials: S
authors.lastname: Angeloni
authors.forename: Manuela
authors.initials: M
authors.lastname: Merli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Carlà
authors.forename: Filippo Maria
authors.initials: FM
authors.lastname: Salvatori
authors.forename: Flavio
authors.initials: F
authors.lastname: Moroni
mesh_terms: D000368:Aged; D000641:Ammonia / Q000097:blood; D005260:Female; D006501:Hepatic Encephalopathy / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007211:Indoles / Q000097:blood* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008102:Liver Circulation; D008103:Liver Cirrhosis / Q000097:blood* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000078183:Oxindoles; D019168:Portasystemic Shunt, Transjugular Intrahepatic / Q000009:adverse effects; D011597:Psychomotor Performance; D013152:Splanchnic Circulation
chemical_list: D007211:Indoles; D000078183:Oxindoles; C022960:2-oxindole; D000641:Ammonia; C030374:indole