skip to main content

SciTech ConnectSciTech Connect

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

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 osmoprotectantsmore » 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.« less
Authors:
;
Publication Date:
OSTI Identifier:
22439699
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 276; Journal Issue: 2; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
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