URSODEOXYCHOLIC ACID REDUCES THE SYSTEMIC TOXICITY OF 1,2-DICHLORO,4-NITROBENZENE BY STIMULATING HEPATIC GLUTATHIONE-S-TRANSFERASE IN MICE

Male C57BL/6 mice were fed with normal diet (ND) or diets containing 0 .3 or 0.5% ursodeoxycholic acid (UDCA) for 3 weeks. Glutathione S-tran sferase (GST) activities in the liver cytosolic fraction of these anim als toward 1,2-dichloro,4-nitrobenzene (DCNB) as well as to 1-chloro,2 ,4-dinitorbenzene (CDNB) were significantly increased in a dose depend ent manner in UDCA-treated groups compared with the control (ND-fed) a nimal group (one-way ANOVA). Reduced glutathione (GSH) levels tended t o slightly decrease with UDCA diets but the different did not attain a statistical significance (P<0.05, one-way ANOVA). Twenty four hr surv ival rates after an oral challenge of 3.5 m/kg of DCNB were significan tly higher (P<0.05, Chi-square test) in the two UDCA fed groups (10/10 for 0.5% group, 8/11 for 0.3% group) compared with the control group (3/11). Thus, UDCA appears to reduce the systemic toxicity of DCNB whi ch is detoxified by the hepatic GST system. Although UDCA has been sho wn to exert hepatoprotective effects in experimental animals and human s in the past, to the best of our knowledge, the present study is the first report that UDCA reduces the systemic toxicity of a toxicant whi ch is detoxified by the hepatic GST system. Although a direct proof is not available, it is most likely that the reduction of the systemic t osicity of DCNB was achieved by the increase in GST activity caused by UDCA feeding. This finding may open a new research field with regard to the unique biological properties of this bile salt in modulating he patic detoxifying enzymes.