title: An hypothesis for a mechanism underlying hepatotoxin-induced hypercreatinuria.
abstract: As part of a wider metabonomic investigation into the early detection and discrimination of site-specific hepatotoxicity, male Sprague-Dawley rats were dosed with the model hepatotoxins allyl formate, ethionine and alpha-naphthylisothiocyanate (ANIT). Urine samples collected pre- and post-dose were examined by (1)H nuclear magnetic resonance (NMR) spectroscopy and the toxin-induced changes in urinary taurine and creatine excretion were quantified. Hypertaurinuria and hypercreatinuria were observed following allyl formate dosing, hypertaurinuria with no change in creatine excretion was observed after ethionine dosing, and hypotaurinuria and hypercreatinuria were observed after ANIT dosing. These changes are indicative of different effects on liver and it has been previously suggested that some hepatotoxin-induced changes in urinary taurine excretion may be due to altered hepatic cysteine utilisation. A related hypothesis is now presented that would explain the selective hypercreatinuria in terms of increased cysteine synthesis.
authors.affiliation: Biological Chemistry, Biomedical Sciences Division, Imperial College of Science, Technology & Medicine, Sir Alexander Fleming Building, South Kensington, SW7 2AZ, London, UK. a.clayton@ic.ac.uk
authors.forename: T Andrew
authors.initials: TA
authors.lastname: Clayton
authors.forename: John C
authors.initials: JC
authors.lastname: Lindon
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Everett
authors.forename: Claude
authors.initials: C
authors.lastname: Charuel
authors.forename: Gilles
authors.initials: G
authors.lastname: Hanton
authors.forename: Jean-Loic
authors.initials: JL
authors.lastname: Le Net
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Provost
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
mesh_terms: D015058:1-Naphthylisothiocyanate / Q000008:administration & dosage / Q000633:toxicity*; D000284:Administration, Oral; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000652:urine*; D003404:Creatinine / Q000652:urine*; D003545:Cysteine / Q000096:biosynthesis*; D004195:Disease Models, Animal; D005001:Ethionine / Q000008:administration & dosage / Q000633:toxicity*; D005563:Formic Acid Esters / Q000008:administration & dosage / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000652:urine
chemical_list: D005563:Formic Acid Esters; D013654:Taurine; D015058:1-Naphthylisothiocyanate; C034499:allyl formate; D003404:Creatinine; D003545:Cysteine; D005001:Ethionine