Hepatotoxin-induced hypertaurinuria: a proton NMR study

Abstract

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.