title: A metabonomic evaluation of the monocrotaline-induced sinusoidal obstruction syndrome (SOS) in rats.
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.
authors.affiliation: University of Mons - UMONS, Department of Human Biology & Toxicology, 20 Place du Parc, 7000 Mons, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Conotte
authors.affiliation: University of Mons - UMONS, Department of Human Biology & Toxicology, 20 Place du Parc, 7000 Mons, Belgium. Electronic address: jean-marie.colet@umons.ac.be.
authors.forename: J-M
authors.initials: JM
authors.lastname: Colet
mesh_terms: D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects; D005978:Glutathione / Q000096:biosynthesis; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced* / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics / Q000379:methods*; D016686:Monocrotaline / Q000633:toxicity*; D009336:Necrosis; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009569:Nitric Oxide; D016686:Monocrotaline; D005978:Glutathione
keywords: (1)H-NMR; Hepatotoxicity; Metabonomic; Monocrotaline; Multivariate data analysis; Sinusoidal obstruction syndrome