title: Utility of a 13C-methacetin breath test in evaluating hepatic injury in rats.
abstract: OBJECTIVE
  Methacetin is thought to be a good substrate for the evaluation of different cytochrome P450 enzymatic systems of liver microsomes because of its rapid metabolism and lack of toxicity in small doses. Recent studies indicate that a methacetin breath test may be a non-invasive alternative for the evaluation of liver function since it correlates well with the severity of liver damage. It may also discriminate between different stages of liver cirrhosis and correlates with the Child-Pugh score. The application of this test in experimental liver damage in animal models has not yet been examined. This study aimed to evaluate the efficacy of the (13)C-methacetin breath test in assessing the extent of hepatic injury in models of acute liver failure, liver cirrhosis, and fatty liver in rats.
  
  
  METHODS
  Absorption of methacetin given per os or intraperitoneally in normal rats was evaluated. The association between liver mass and (13)C-methacetin breath test results was assessed in a 70% hepatectomy rat model. Fulminant hepatic failure was induced by three consecutive intraperitoneal injections of thioacetamide, 300 mg/kg, at 24 h intervals. For induction of liver cirrhosis, rats were given intraperitoneal injections of thioacetamide, 200 mg/kg, twice a week for 12 weeks. A methionine-choline deficient diet was used for the induction of fatty liver. Rats were analyzed for (13)C-methacetin by BreathID (MBID) using molecular correlation spectrometry. BreathID continuously sampled the animal's breath for 60 min and displayed the results on the BreathID screen in real-time.
  
  
  RESULTS
  Methacetin was absorbed well irrespective of the administration method in normal rats. Liver mass was associated with peak amplitude, complete percent dose recovery (CPDR) at 30 and 60 min and MBID peak time. A high degree of association was also demonstrated with MBID results in acute hepatitis (peak amplitude, 19.6 +/- 3.4 vs 6.3 +/- 1.63.4; CPDR30, 6.0 +/- 3.3 vs 1.2 +/- 0.5; CPDR60, 13.3 +/- 4.5 vs 3.2 +/- 1.4; and peak time, 31.0 +/- 14.9 vs 46.9 +/- 10.8 min) and liver cirrhosis (peak amplitude, 24.4 +/- 2.3 vs 15.6 +/- 6.4; CPDR30, 7.9 +/- 1.2 vs 2.7 +/- 1.0; CPDR60, 17.8 +/- 2.6 vs 8.8 +/- 2.1; and peak time, 30.2 +/- 1.5 vs 59.6 +/- 14.5 min), but not with grade of liver steatosis.
  
  
  CONCLUSIONS
  Methacetin is well absorbed and exclusively metabolized in the liver. MBID is a sensitive test and may be a useful tool for the evaluation of functional liver mass in animal models of acute liver failure and cirrhosis. However, MBID could not distinguish between fatty liver and normal liver in rats.
authors.affiliation: Department of Gastroenterology, The E. Wolfson Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. shirin@wolfson.health.gov.il
authors.forename: Haim
authors.initials: H
authors.lastname: Shirin
authors.forename: Hussein
authors.initials: H
authors.lastname: Aeed
authors.forename: Tamar
authors.initials: T
authors.lastname: Shalev
authors.forename: Vladimir
authors.initials: V
authors.lastname: Sorin
authors.forename: Svetlana
authors.initials: S
authors.lastname: Stavinski
authors.forename: Mark
authors.initials: M
authors.lastname: Shahmurov
authors.forename: Yaron
authors.initials: Y
authors.lastname: Ilan
authors.forename: Yona
authors.initials: Y
authors.lastname: Avni
mesh_terms: D000081:Acetamides / Q000008:administration & dosage; D000284:Administration, Oral; D000818:Animals; D001944:Breath Tests; D002247:Carbon Isotopes; D002796:Choline Deficiency / Q000150:complications; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology; D006498:Hepatectomy; D007274:Injections, Intraperitoneal; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000175:diagnosis* / Q000473:pathology; D017114:Liver Failure, Acute / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D008715:Methionine / Q000172:deficiency; D009929:Organ Size; D011237:Predictive Value of Tests; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D013853:Thioacetamide; D013997:Time Factors
chemical_list: D000081:Acetamides; D002247:Carbon Isotopes; D013853:Thioacetamide; C035495:methacetin; D008715:Methionine