Suppression by Chai-hu-gui-zhi-tang of the development of liver lesions induced by N-nitrosomorpholine in Sprague-Dawley rats

The effects of Chai-hu-gui-zhi-tang (TJ-10) on the development of liver les ions induced by N-nitrosomorpholine and on labeling and apoptotic indices w ere investigated in male Sprague-Dawley rats. Rats were given chow pellets containing 0.5 or 1.0% TJ-10 and, from the beginning of the experiment, wer e given drinking water containing N-nitrosomorpholine for 8 weeks. Visible white liver nodules, cellular alteration foci, and hepatic foci staining po sitively for glutathione-S-transferase, placental type, were examined macro scopically or histochemically. In week 16, TJ-10 at both dosages significan tly reduced the incidence, and/or number of visible white nodules and hepat ic lesions. Quantitative histologic analysis also showed that prolonged fee ding of TJ-10 at both dosages significantly reduced the number of hepatic f oci positive for glutathione-S-transferase, placental type. Administration of TJ-10 at both dosages also significantly decreased the labeling index of adjacent liver and significantly increased the apoptotic index of adjacent liver but had no significant effect on those of neoplastic lesions. These findings indicate that TJ-10 suppresses the development of liver lesions an d suggest that this effect might be related to TJ-10's inhibition of cell p roliferation and induction of apoptosis in adjacent hepatocytes. (C) 2000 E lsevier Science Ireland Ltd. All rights reserved.