Hepatotoxin-induced hypertaurinuria: a proton NMR study.
The urinary excretion of taurine by rats after dosing with various hepatotoxins has been investigated by 1H NMR spectroscopy. After single hepatotoxic doses of hydrazine, carbon tetrachloride, 1-naphthylisothiocyanate, or thioacetamide there was biochemical and histopathological evidence of hepatic damage. Proton NMR spectroscopy of the urine collected for 24 h after dosing from these animals revealed a marked elevation in taurine (control 11.9 mumole/h/kg) after dosing with thioacetamide (42.2 mumole/h/kg), carbon tetrachloride (52.5 mumole/h/kg), 1-naphthyl-isothiocyanate (80.4 mumole/h/kg) and hydrazine (52.9 mumole/h/kg). After allyl alcohol administration there was no increase in taurine excretion (7.5 mumol/h/kg). The excretion of taurine after hydrazine administration was dose related. High resolution proton NMR spectroscopic analysis of urine also revealed resonances from several metabolites of hydrazine, an N-acetylcysteine conjugate of allyl alcohol, and acetamide as a metabolite of thioacetamide after dosing with the respective compounds. Changes in endogenous substances that may be related to the pathological events were also detected, such as a decrease in the excretion of 2-oxoglutarate and citrate after both hydrazine and carbon tetrachloride administration. The results confirm that proton NMR spectroscopic analysis of urine is a powerful analytical tool for the evaluation and study of toxic substances. Furthermore, measurement of urinary taurine may provide a non-invasive indicator of acute hepatic damage with certain classes of hepatotoxins.
Sanins
S M
SM
Chemistry Department, Birkbeck College, London, UK.
Nicholson
J K
JK
Elcombe
C
C
Timbrell
J A
JA
D015058:1-Naphthylisothiocyanate / Q000633:toxicity; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002252:Carbon Tetrachloride Poisoning / Q000652:urine; D056486:Chemical and Drug Induced Liver Injury / Q000652:urine*; D006834:Hydrazines / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011522:Protons; D051381:Rats; D013654:Taurine / Q000652:urine*; D013853:Thioacetamide / Q000633:toxicity
D006834:Hydrazines; D011522:Protons; D013853:Thioacetamide; D013654:Taurine; C029424:hydrazine; D015058:1-Naphthylisothiocyanate; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin