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Evaluation of the 13C-Octanoate Breath Test as a Surrogate Marker of Liver Damage in Animal Models

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Abstract

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 β-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.

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Abbreviations

CPDR:

Complete percentage dose recovery

OBT:

Octanoate breath test

IRMS:

Isotope ratio mass spectrometer

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Acknowledgments

This work was supported by Exalenz Ltd.

Conflict of interest statement

Prof. Yaron Ilan is the Medical Director of Exalenz.

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Authors and Affiliations

  1. Department of Gastroenterology, The E. Wolfson Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Tamar Shalev, Hussein Aeed & Yona Avni

  2. Department of Surgery, The E. Wolfson Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Vladimir Sorin

  3. Department of Pathology, The E. Wolfson Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Mark Shahmurov & Elena Didkovsky

  4. Gastroenterology and Liver Units, Department of Internal Medicine, Hadassah Medical Center, Hebrew University, Jerusalem, Israel

    Yaron Ilan

  5. Gastroenterology Unit, Hasharon Hospital, Rabin Medical Center, Tel-Aviv University, Tel-Aviv, Israel

    Haim Shirin

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  1. Tamar Shalev
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  2. Hussein Aeed
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  3. Vladimir Sorin
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Correspondence to Haim Shirin.

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Shalev, T., Aeed, H., Sorin, V. et al. Evaluation of the 13C-Octanoate Breath Test as a Surrogate Marker of Liver Damage in Animal Models. Dig Dis Sci 55, 1589–1598 (2010). https://doi.org/10.1007/s10620-009-0913-2

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  • DOI: https://doi.org/10.1007/s10620-009-0913-2

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