Effect of ovarian hormones upon liver mitochondrial function in diabetic rats

In the present study it is shown that streptozotocin (SZ)-induced chronic diabetes of female albino rats produced significant alterations in liver mitochondrial function after 30-35 days of diabetes. The disturbances were as follows: (1) a significant fall of the mean values of the respiratory control ratio and of state 3 of respiration using three substrates, 3-hydroxybutyrate, malate-glutamate and succinate, and (2) a significant increase of the mean damping factor of the oscillatory osmotic variations (with valinomycin as K+ ionophore and succinate as substrate). The same mitochondrial function parameters were analyzed for comparison in control non-diabetic rats (group N) and in the following groups of female rats with chronic diabetes: intact (group I), oophorectomized (6 days after the injection of SZ) (group O), and oophorectomized with restitution therapy of 17 beta-estradiol (from the operation until the day before killing) (group O + Eol). The O group showed significantly higher values of the respiratory control ratio and of state 3 of respiration and significantly lower damping factors than group I. The restitution treatment in the O + Eol group restored the mitochondrial functions assayed to values similar to those of group I. These data provide strong evidence that estrogens exert a negative effect at the molecular level upon impaired liver mitochondrial functions in SZ-induced diabetes.