Favourable, 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 38486 upon the hepatic mitochondrial function of diabetic rats has been studied. At the same time, the action of adrenalectomy and corticosterone restitution on this function were comparatively demonstrated. The parameters measured were oxygen consumption with the substrates: 3-hydroxybutyrate (HB), succinate (Suc) and malate-glutamate (Mal-glut) in intact liver mitochondria and the activities of 3-hydroxybutyrate dehydrogenase (HBD) and cytochrome c oxidase (Cyt.c oxid.) enzymes in broken liver mitochondria. The groups of animals studied were normal controls (N) and the following groups of diabetic rats: rats without any treatment (D), adrenalectomized rats (D+ADX), rats that were adrenalectomized and treated with corticosterone (D+ADX+C) and four groups treated with increasing oral doses of RU (in mg/kg body wt.), that is, 12.5 (D+RU1), 25.0 (D+RU2), 37.5 (D+RU3) and 50.0 (D+RU4). The results showed a tendency of increasing values of mitochondrial oxygen consumption in diabetic animals treated with RU. The favourable effect of increasing doses of RU on O2 consumption of diabetic rat liver mitochondria with each of the substrates showed a significant association as indicated by the values obtained for the correlation coefficients r (0.95, 0.97 and 0.99 according to the substrate HB, Succ or Mal-glut, respectively). Likewise, the correlation between the treatment with increasing doses of RU and the recovery of enzyme activities showed a significant dose-effect association with r 0.94 for HBD and r = 0.95 for 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 diabetic rats was demonstrated by the dose-dependent treatment with RU as seen by the correlation statistical study performed. At the same time, the pernicious effect that glucocorticoids exert upon such function in experimental diabetes was confirmed.
Brignone
J A
JA
Departamento de Bioquímica, Facultad de Medicina, Universidad de Buenos Aires, Argentina, Paraguay.
de Brignone
C M
CM
Ricci
C R
CR
de Mignone
I R
IR
Susemihl
M C
MC
Rodríguez
R R
RR
D020155:3-Hydroxybutyric Acid; D000315:Adrenalectomy; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D003576:Electron Transport Complex IV / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology*; D006884:Hydroxybutyrate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D006885:Hydroxybutyrates / Q000378:metabolism; D008293:Malates / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology*; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid
D000893:Anti-Inflammatory Agents; D006727:Hormone Antagonists; D006885:Hydroxybutyrates; D008293:Malates; D013386:Succinates; D015735:Mifepristone; D019802:Succinic Acid; D006884:Hydroxybutyrate Dehydrogenase; D003576:Electron Transport Complex IV; D020155:3-Hydroxybutyric Acid; D003345:Corticosterone