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 hepatocellular damage. This diabetes-induced change was associated with a marked impairment in the hepatic glutathione antioxidant/detoxification response to CCl4 challenge, as indicated by the abrogation of the increases in hepatic reduced glutathione (GSH) level, glucose-6-phosphate dehydrogenase and microsomal glutathione S-transferases (GST) activities upon challenge with increasing doses of CCl4. While the hepatic GSH level was increased in diabetic rats, the hepatic mitochondrial GSH level and Se-glutathione peroxidase activity were significantly reduced. Insulin treatment could reverse most of the biochemical alterations induced by diabetes. Both insulin and schisandrin B (Sch B) pretreatments protected against the CCl4 hepatotoxicity in diabetic rats. The hepatoprotection was associated with improvement in hepatic glutathione redox status in both cytosolic and mitochondrial compartments, as well as the increases in hepatic ascorbic acid level and microsomal GST activity. The ensemble of results suggests that the diabetes-induced impairment in hepatic mitochondrial glutathione redox status may at least in part be attributed to the enhanced susceptibility to CCl4 hepatotoxicity. Sch B may be a useful hepatoprotective agent against xenobiotics-induced toxicity under the diabetic conditions.
Mak
D H
DH
Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong.
Ko
K M
KM
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001786:Blood Glucose; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D034242:Cyclooctanes; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D017705:Lignans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D008861:Microsomes / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D011083:Polycyclic Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
D000975:Antioxidants; D001786:Blood Glucose; D034242:Cyclooctanes; D007328:Insulin; D017705:Lignans; D011083:Polycyclic Compounds; C015499:schizandrin B; D013311:Streptozocin; D002251:Carbon Tetrachloride; D005954:Glucosephosphate Dehydrogenase; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D000410:Alanine Transaminase; D005978:Glutathione