ALTERATIONS IN SUSCEPTIBILITY TO CARBON-TETRACHLORIDE TOXICITY AND HEPATIC ANTIOXIDANT DETOXIFICATION SYSTEM IN STREPTOZOTOCIN-INDUCED SHORT-TERM DIABETIC RATS - EFFECTS OF INSULIN AND SCHISANDRIN-B TREATMENT/

The streptozotocin-induced short-term (2 week) diabetic rats showed an increase in susceptibility to carbon tetrachloride (CCl4)-induced hep atocellular damage. This diabetes-induced change was associated with a marked impairment in the hepatic glutathione antioxidant/detoxificati on response to CCl4, challenge, as indicated by the abrogation of the increases in hepatic reduced glutathione (GSH) level, glucose-6-phosph ate dehydrogenase and microsomal glutathione S-transferases (GST) acti vities upon challenge with increasing doses of CCl4. While the hepatic GSH level was increased in diabetic rats, the hepatic mitochondrial G SH level and Se-glutathione peroxidase activity were significantly red uced. Insulin treatment could reverse most of the biochemical alterati ons induced by diabetes. Both insulin and schisandrin B (Sch B) pretre atments protected against the CCl4 hepatotoxicity in diabetic rats. Th e hepatoprotection was associated with improvement in hepatic glutathi one redox status in both cytosolic and mitochondrial compartments, as well as the increases in hepatic ascorbic acid level and microsomal GS T activity. The ensemble of results suggests that the diabetes-induced impairment in hepatic mitochondrial glutathione redox status may at l east in part be attributed to the enhanced susceptibility to CCl4 hepa totoxicity. Sch B may be a useful hepatoprotective agent against xenob iotics-induced toxicity under the diabetic conditions.