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.