Hepatotoxin-induced hypertaurinuria: a proton NMR study

Abstract

The urinary excretion of taurine by rats after dosing with various hepatotoxins has been investigated by¹H 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 μmole/h/kg) after dosing with thioacetamide (42.2 μmole/h/kg), carbon tetrachloride (52.5 gmmole/ h/kg), 1-naphthyl-isothiocyanate (80.4 μmole/h/kg) and hydrazine (52.9 μmmole/h/kg). After allyl alcohol administration there was no increase in taurine excretion (7.5 μmol/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.