Abstract B18

Oxidative molecular damage and glutathione S-transferase induced by a choline-deficient diet in the rat liver
S. C. Sahu, S. Satchithanandam, M. A. Bryant, and S. R. Blakely. CFSAN, Food and Drug Administration. Washington, DC

A choline-deficient (CD) diet leads to liver dysfunction in humans and hepatocarcinoma in rats. It is hypothesized that oxidative stress is involved in this process. Two cellular antioxidants, glutathione (GSH) and glutathione S-transferase (GST), play major roles in the detoxification of carcinogens. The placental GST (GST-P), which is not found in the normal adult rat liver, is present in highly elevated levels in hepatic preneoplastic foci and hepatocarcinoma. This study was undertaken to investigate what effects, if any, the CD diet has on the hepatic antioxidants (GSH and GST), GST-P, and macromolecules (proteins and lipids). The control and treated groups of F344 rats were fed the CS (choline-sufficient) and CD diets, respectively, for 12 weeks. The level of hepatic GST-P, induced by the CD diet only, was quantitated by ELISA. In hematoxylene and eosin stained liver sections from the CD rats diffuse fatty change was present. When compared with the CS rats, decreased levels of hepatic GSH and total proteins concurrent with increased levels of oxidized proteins, lipid peroxides, GST-P and GST activity were observed in the CD rats. The results indicate strong pro-oxidant activity of the CD diet in rat liver.