FAVORABLE, SIGNIFICANT EFFECT OF THE DOSE-DEPENDENT TREATMENT WITH RU-38486 (RU) ON THE ALTERATIONS OF THE HEPATIC MITOCHONDRIAL-FUNCTION OF DIABETIC RATS

In the present work, the effect 'in vivo' of increasing doses of RU 38 486 upon the hepatic mitochondrial function of diabetic rats has been studied. At the same time, the action of adrenalectomy and corticoster one restitution on this function were comparatively demonstrated. The parameters measured were oxygen consumption with the substrates: 3-hyd roxybutyrate (HE), succinate (Sue) and malate-glutamate (Mal-glut) in intact liver mitochondria and the activities of 3-hydroxybutyrate dehy drogenase (HBD) and cytochrome c oxidase (Cyt.c oxid.) enzymes in brok en liver mitochondria. The groups of animals studied were normal contr ols (N) and the following groups of diabetic rats: rats without any tr eatment (D), adrenalectomized rats (D+ADX), rats that were adrenalecto mized and treated with corticosterone (D+ADX+C) and four groups treate d with increasing oral doses of RU (in mg/kg body wt.), that is. 12.5 (D+RU(1)), 25.0 (D+RU(2)), 37.5 (D+RU(3)) and 50.0 (D+RU(4)). The resu lts showed a tendency of increasing values of mitochondrial oxygen con sumption in diabetic animals treated with RU. The favourable effect of increasing doses of RU on O-2 consumption of diabetic rat liver mitoc hondria with each of the substrates showed a significant association a s indicated by the values obtained for the correlation coefficients r (0.95, 0.97 and 0.99 according to the substrate HE, Succ or Mal-glut, respectively). Likewise, the correlation between the treatment with in creasing doses of RU and the recovery of enzyme activities showed a si gnificant dose-effect association with r = 0.94 for HBD and r = 0.95 f or Cyt.c oxid. Adrenalectomy showed a similar effect to treatment with the maximum dose of RU while corticosterone restitution gave measured values similar to those of the D group. In conclusion, the favourable , significant variation of the hepatic mitochondrial function of diabe tic rats was demonstrated by the dose-dependent treatment with RU as s een by the correlation statistical study performed. At the same time, the pernicious effect that glucocorticoids exert upon such function in experimental diabetes was confirmed.