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

Journal Article · Tue Apr 15 04:00:00 EDT 2014 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2014.02.008· OSTI ID:22439699

Conotte, R.

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. {sup 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. - Highlights: • Urine metabonomic profiles of SOS have been identified. • Urine osmoprotectants and anti-oxidants indicated an initial liver protection. • Liver necrosis was demonstrated by increased urine levels of taurine and creatine. • NO depletion was suggested by changes in ornithine and urea.

• OSTI ID: 22439699
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 2 Vol. 276; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BETAINE
BIOLOGICAL MARKERS
BIOPSY
CHEMOTHERAPY
CREATINE
DATA ANALYSIS
DIAGNOSIS
LIVER
METASTASES
NECROSIS
NEOPLASMS
NUCLEAR MAGNETIC RESONANCE
ORNITHINE
RATS
SARCOSINE
TAURINE
TOXICITY
UREA
URINE