Changes in taurine as an indicator of hepatic dysfunction and biochemical perturbations. Studies in vivo and in vitro.
We have shown that urinary taurine level may be used as a biomarker of pathological and biochemical lesions. Detection of changes in the urinary concentration of this low molecular weight metabolite indicates biochemical lesions which may also be associated with pathological damage. Hepatotoxic compounds such as CCl4, galactosamine and thioacetamide that cause hepatic necrosis and compounds such as hydrazine and ethionine that cause fatty liver all result in elevated urinary taurine levels in rats. However compounds which do not cause liver damage, such as cycloheximide, also raise urinary taurine levels. All of these substances are known to or are believed to inhibit protein synthesis. Conversely, compounds which increase protein synthesis, such as phenobarbital and clenbuterol, significantly decrease urinary taurine levels. Compounds which interfere with hepatic GSH synthesis will also change urinary taurine levels. Thus, depletion of GSH with diethyl maleate or phorone decreases urinary taurine whereas inhibition of GSH synthesis with compounds such as buthionine sulphoximine increases urinary taurine levels. In isolated hepatocytes in vitro, leakage of taurine occurs in response to cytotoxic compounds such as hydrazine and allyl alcohol. However, total taurine levels were increased by the hepatotoxicant CCl4. Taurine synthesis is decreased by depletion of GSH with allyl alcohol in isolated hepatocytes. Therefore taurine levels are an important potential biomarker for biochemical lesions induced by chemicals both in vivo and in vitro, in particular changes in protein and GSH synthesis.
Timbrell
J A
JA
Toxicology Department, School of Pharmacy, London, United Kingdom.
Waterfield
C J
CJ
D000818:Animals; D015415:Biomarkers / Q000652:urine; D002251:Carbon Tetrachloride / Q000633:toxicity; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D002976:Clenbuterol / Q000494:pharmacology; D005688:Galactosamine / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D007659:Ketones / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008107:Liver Diseases / Q000175:diagnosis / Q000473:pathology* / Q000652:urine; D008297:Male; D008298:Maleates / Q000494:pharmacology; D009336:Necrosis; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000378:metabolism* / Q000652:urine; D013853:Thioacetamide / Q000633:toxicity
D015415:Biomarkers; D007659:Ketones; D008298:Maleates; D013853:Thioacetamide; D013654:Taurine; D005688:Galactosamine; C018637:phorone; D002251:Carbon Tetrachloride; C014476:diethyl maleate; D005978:Glutathione; D002976:Clenbuterol; D010634:Phenobarbital