EVALUATION OF URINARY BIOMARKERS FOR RADICAL-INDUCED LIVER-DAMAGE IN RATS TREATED WITH CARBON-TETRACHLORIDE

Carbon tetrachloride (CCl4) is a model compound for inducing free radi cal damage in liver. In this study 10 biomarkers in rats treated ip wi th three different single doses of CCl4 (0.25, 0.50, and 1.00 ml/kg bo dy wt) were measured dose and time dependently and compared to evaluat e these urinary products as noninvasive biomarkers for radical damage. Eight degradation products of lipid peroxides, namely, formaldehyde, acetaldehyde, acetone, propanal, butanal, pentanal, hexanal, and malon dialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and coproporph yrin III were measured in this study. As general measures of toxicity, several clinical chemical parameters (n = 12) and histopathoIogical d amage were determined. A dose-dependent increase in both the clinical parameters and the lipid degradation products was found. Increases in lipid degradation products were statistically significant at doses of 0.5 and 1 ml/kg CCl4(.) An increase in these products was already foun d in the first 12 h after exposure. At the lowest dose, 0.25 ml/kg CCl 4, acetaldehyde and propanal already showed a statistically significan t increase as well. No change in the urinary levels of 8-OH-dG could b e found in this study and a decrease in the urinary excretion of copro porphyrin III was found. It is concluded that 8-OH-dG and coproporphyr in III are not useful biomarkers for radical damage induced by CCl4(.) Lipid degradation products, however, are promising noninvasive biomar kers for in vivo radical damage, although the precise specificity of t hese biomarkers for damage induced by radicals needs to be further inv estigated. (C) 1998 Academic Press.