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A metabonomic evaluation of the monocrotaline-induced sinusoidal obstruction syndrome (SOS) in rats

Conotte, R., Colet, J.-M.·2014·Toxicology and Applied Pharmacology
DOI 10.1016/j.taap.2014.02.008
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Abstract

The main curative treatment of colorectal cancer remains the surgery. However, when metastases are suspected, surgery is followed by a preventive chemotherapy using oxaliplatin which, unfortunately, may cause liver sinusoidal obstruction syndrome (SOS). Such hepatic damage is barely detected during or after chemotherapy due to a lack of effective diagnostic procedures, but liver biopsy. The primary objective of the present study was to identify potential early diagnosis biomarkers of SOS using a metabonomic approach. SOS was induced in rats by monocrotaline, a prototypical toxic substance. (1)H NMR spectroscopy analysis of urine samples collected from rats treated with monocrotaline showed significant metabolic changes as compared to controls. During a first phase, cellular protective mechanisms such as an increased synthesis of GSH (reduced taurine) and the recruitment of cell osmolytes in the liver (betaine) were seen. In the second phase, the disturbance of the urea cycle (increased ornithine and urea reduction) leading to the depletion of NO, the alteration in the GSH synthesis (increased creatine and GSH precursors (glutamate, dimethylglycine and sarcosine)), and the liver necrosis (decrease taurine and increase creatine) all indicate the development of SOS.

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Metadata

Authors
Conotte, R., & Colet, J.-M.
ORCID
Conotte, R.
Venue
Toxicology and Applied Pharmacology
Publisher
Elsevier BV
Published
2014-04
Volume
276
Issue
2
Pages
147-156
ISSN
0041-008X
DOI
10.1016/j.taap.2014.02.008
Cited by
19
References
0
Language
en

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