ROLE OF THIOL HOMEOSTASIS AND ADENINE-NUCLEOTIDE METABOLISM IN THE PROTECTIVE EFFECTS OF FRUCTOSE IN QUINONE-INDUCED CYTOTOXICITY IN RAT HEPATOCYTES

Freshly-isolated rat hepatocytes were exposed in glucose (15 mM) or fr uctose (5 mM) medium to menadione (2-methyl-1,4-naphthoquinone) (85 mu M) or 1,4-naphthoquinone (NQ) (50 mu M). Menadione and NQ are closely related quinones and have an approximately equal potential to induce redox cycling. However, NQ has a higher potential to arylate and is mo re toxic than menadione. During 2 hr of incubation, cell viability, th iol status, adenine nucleotide level and lactate production were deter mined. LDH-leakage was used as a measure of cell viability. In glucose medium, exposure of hepatocytes to menadione or NQ resulted in a fast er excretion rate of oxidized glutathione as compared to those cells i n fructose medium. As a result, quinone-exposed hepatocytes in fructos e medium retained higher amounts of oxidized glutathione. Menadione-ex posed hepatocytes in fructose medium exhibited a diminished rate of tr ansthiolation of protein thiols with oxidized glutathione as compared to those cells in glucose medium. The adenine nucleotide level of hepa tocytes in glucose medium was markedly higher than in fructose medium. This was caused by an ATP decrease in hepatocytes in fructose medium resulting in a low energy charge (E.C.) (0.6) as compared to hepatocyt es in glucose medium (0.9). Only menadione caused a decrease in the E. C. in glucose medium while NQ caused a decrease of all three adenine n ucleotides. In fructose medium, quinone-exposed hepatocytes showed no change in their adenine nucleotides as compared to control cells. Desp ite the higher oxidized glutathione content and the lower ATP level of NQ-exposed hepatocytes in fructose medium, they had a better Viabilit y than those cells in glucose medium. From our results we conclude tha t a high ATP content is not always beneficial for sell survival.