Evaluation of the 13C-octanoate breath test as a surrogate marker of liver damage in animal models.
BACKGROUND
Octanoate (also known as sodium octanoate), a medium-chain fatty acid metabolized in the liver, is a potential substrate for non-invasive breath testing of hepatic mitochondrial beta-oxidation.


METHODS
We evaluated the 13C-octanoate breath test (OBT) for assessing injury in acute hepatitis and two rat models of liver cirrhosis, first testing octanoate absorption (per os or intraperitoneally (i.p.)) in normal rats. We then induced acute hepatitis with thioacetamide (300 mg/kg/i.p., 24-h intervals). Liver injury end points were serum aminotransferase levels and 13C-OBT (24 and 48 h following initial injection). Thioacetamide (200 mg/kg/i.p., twice per week, 12 weeks) was used to induce liver cirrhosis. OBT and liver histological assessment were performed every 4 weeks. Bile duct ligation (BDL) was used to induce cholestatic liver injury. We completed breath tests with 13C-OBT and 13C-methacetin (MBID), liver biochemistry, and liver histology in BDL and sham-operated rats (baseline, 6, 14, 20 days post-BDL).


RESULTS
Octanoate absorbs well by either route. Peak amplitudes and cumulative percentage dose recovered at 30 and 60 min (CPDR30/60), but not peak time, correlated with acute hepatitis. Fibrosis stage 3 at week 8 significantly correlated with each OBT parameter. Cholestatic liver injury (serum bilirubin, ALP, gamma-GT, liver histology) was associated with significant suppression of the maximal peak values and CPDR30/60, respectively (P<0.05),using MBID but not 13C-octanoate.


CONCLUSIONS
OBT is sensitive for potentially evaluating liver function in rat models of acute hepatitis and thioacetamide-induced liver cirrhosis but not in cholestatic liver injury. The MBID test may be better for evaluation of cholestatic liver disease in this model.
Shalev
Tamar
T
Department of Gastroenterology, The E. Wolfson Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. tamars@wolfson.health.gov.il
Aeed
Hussein
H
Sorin
Vladimir
V
Shahmurov
Mark
M
Didkovsky
Elena
E
Ilan
Yaron
Y
Avni
Yona
Y
Shirin
Haim
H
D000081:Acetamides; D000208:Acute Disease; D000818:Animals; D001944:Breath Tests; D002210:Caprylates; D002245:Carbon Dioxide / Q000378:metabolism; D002247:Carbon Isotopes; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D001651:Cholestasis, Extrahepatic / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D003135:Common Bile Duct / Q000601:surgery; D004195:Disease Models, Animal; D008026:Ligation; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D008297:Male; D011237:Predictive Value of Tests; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide; D013997:Time Factors
D000081:Acetamides; D002210:Caprylates; D002247:Carbon Isotopes; D013853:Thioacetamide; C035495:methacetin; D002245:Carbon Dioxide; C031492:octanoic acid