RESUMEN
Chronic diabetes induced by the injection of streptozotocin in male and female albino adult rats provoked significant alteration of liver mitochondrial function 30 or 35 days after administration of the drug. Thus, we obtained mean values of respiratory control (RC) and state 3 (S3) with 3-hydroxybutyrate as substrate 40 or 50
lower than those of non-diabetic animals. With other substrates (malate-glutamate, succinate) the decrease of RC and S3 in the diabetic animals was 20
or 30
of the normal mean values. The osmotic damped oscillations of mitochondria were measured as another parameter of the organella function. It was assayed with valinomycin as K+ ionophore and succinate as substrate. In diabetic rats of both sexes we found a significant increase of the mean damping factor of these oscillatory variations compared with normal values. The above-mentioned results indicate a lesser elasticity and an impaired K+ transport of mitochondria across the inner membrane in diabetic animals. Both reported parameters, respiration and oscillatory variations of liver mitochondria, were measured in normal non-diabetic rats and in the groups of diabetic rats referred to as follows: 1) intact (male and female), 2) gonadectomized (male and female), 3) oophorectomized with restitution of 17 beta-estradiol. Ovariectomized diabetic rats showed a significant increase in the values of the RC and S3 of liver mitochondria compared with intact female diabetic animals. The withdrawal of the ovarian hormone in female diabetic rats significantly decreased the values of the damping factors of the oscillatory mechanism and they were similar to the normal. The restitution of 17 beta-estradiol to oophorectomized diabetic rats resulted in a decrease of liver mitochondrial respiration. The damping factor of liver mitochondria of the oophorectomized diabetic rats treated with the estrogen showed values significantly higher than those of female diabetic animals without the hormone and similar to the values of the intact diabetic female rats. Castration of male rats did not produce any effect upon the liver mitochondrial RC and S3 or upon the mean damping factor of the oscillatory variation either. Then the castration of male diabetic rats did not modify the mitochondrial function. In contrast, the oophorectomy of diabetic animals produced amelioration of mitochondrial respiration and oscillatory behavior. The conclusion is drawn that in female rats the circulating 17 beta-estradiol produced a pernicious effect upon liver mitochondrial function in the experimental diabetic state.
RESUMEN
The present work studied the effect of cold on oxygen consumption (OC) and alpha-glycerophosphate dehydrogenase activity (alpha-GPD) in heart mitochondria of hypothyroid rats (hypo) treated with T3, T4 or T4 plus Iopanoic Acid (IOP). 200 g male Wistar rats were made hypothyroid by 131I administration. Animals were injected s.c., in divided doses, for 10 days, with one of the following substances: T3, 300 ng/100 g BW/day; T4, 2 micrograms/100 g BW/day or T4 plus IOP, 5 mg/100 g BW/day, for 72 h preceding the experiment. One half of each group was housed in a cold room at 4 degrees C and the other at 22 degrees C, for 25 h, and thereafter decapitated. Heart mitochondria were isolated by routine methods. The OC was measured polarographically using L-malate, L-glutamate and malonate as substrates. Intramitochondrial alpha-GPD activity was measured by a microcolorimetric assay. The results from 16 or 20 rats/group (4 or 5 pools of 4 hearts each) were: In the rats kept at 22 degrees C the OC (in ng at. oxyg./min/mg prot.; State 3) in the hypo+T4 group was 69 +/- 10; in the rats treated with T4+IOP, 75 +/- 11 and in the hypo+T3, 102 +/- 5. When the animals were exposed to 4 degrees C no change was observed in the hypo+T4 and hypo+T4IOP groups. On the other hand, OC was significantly lower in the T3-treated animals (p less than 0.001, versus their controls at 22 degrees C). This group of rats did not survive when exposed to cold.(ABSTRACT TRUNCATED AT 250 WORDS)
RESUMEN
In the present work the effects of corticosterone restitution were examined in female rats with chronic streptozotocin (SZ)-induced diabetes upon intact liver mitochondrial function and the activities of 3-hydroxybutyrate dehydrogenase (HBD), succinate dehydrogenase (SD) and cytochrome c oxidase (Cox) of the ruptured organelle. The liver mitochondrial function was analyzed by the respiration and the osmotic oscillatory behaviour. Respiration was measured by polarographic method and both the state 3 of active respiration (S3) and the respiratory control (RC) were determined using the following substrates: 3-hydroxybutyrate, succinate and malate-glutamate. The oscillatory behaviour was measured using as parameters the damping factors (DF) which are the ratios of amplitudes of two consecutive peaks or troughs of the spectrophotometrical tracings of this phenomenon. A group of control normal rats (N) and the following three groups of diabetic rats were studied: controls (D), adrenalectomized (D + ADX) and adrenalectomized with corticosterone restitution (D + ADX + C). The results of mitochondrial respiration showed that the mean values of S3 and RC decreased with the three substrates in the group D + ADX + C compared with D + ADX group (p < 0.001). This group demonstrated a significant increase of S3 and RC values of the respiration compared with the D group. The oscillatory behaviour of liver mitochondria of D + ADX + C group demonstrated a significant increase in the DF of peaks and troughs compared with D + ADX group. The values of DF of the latter group were not significantly different from the N group. The behaviour of the enzymes activities of ruptured liver mitochondria were different for each enzyme in the different groups of treated rats. Thus, in the D + ADX + C group the mean value of the activity of HBD significantly decreased, that of the Cox increased (p < 0.02) and that of SD did not show any variation compared with the corresponding values of the D + ADX group. Likewise, the mean value of HBD activity in this latter group was similar to that of the N group and that of Cox activity was lesser (p < 0.01) than that of the D group. The conclusion is drawn that corticosterone has significant additional diabetogenic effects upon biochemical functions of liver mitochondria in the SZ-induced diabetic state which could occur through the hormone cellular receptors.
RESUMEN
In the present work the effects of corticosterone restitution were examined in female rats with chronic streptozotocin (SZ)-induced diabetes upon intact liver mitochondrial function and the activities of 3-hydroxybutyrate dehydrogenase (HBD), succinate dehydrogenase (SD) and cytochrome c oxidase (Cox) of the ruptured organelle. The liver mitochondrial function was analyzed by the respiration and the osmotic oscillatory behaviour. Respiration was measured by polarographic method and both the state 3 of active respiration (S3) and the respiratory control (RC) were determined using the following substrates: 3-hydroxybutyrate, succinate and malate-glutamate. The oscillatory behaviour was measured using as parameters the damping factors (DF) which are the ratios of amplitudes of two consecutive peaks or troughs of the spectrophotometrical tracings of this phenomenon. A group of control normal rats (N) and the following three groups of diabetic rats were studied: controls (D), adrenalectomized (D + ADX) and adrenalectomized with corticosterone restitution (D + ADX + C). The results of mitochondrial respiration showed that the mean values of S3 and RC decreased with the three substrates in the group D + ADX + C compared with D + ADX group (p < 0.001). This group demonstrated a significant increase of S3 and RC values of the respiration compared with the D group. The oscillatory behaviour of liver mitochondria of D + ADX + C group demonstrated a significant increase in the DF of peaks and troughs compared with D + ADX group. The values of DF of the latter group were not significantly different from the N group. The behaviour of the enzymes activities of ruptured liver mitochondria were different for each enzyme in the different groups of treated rats. Thus, in the D + ADX + C group the mean value of the activity of HBD significantly decreased, that of the Cox increased (p < 0.02) and that of SD did not show any variation compared with the corresponding values of the D + ADX group. Likewise, the mean value of HBD activity in this latter group was similar to that of the N group and that of Cox activity was lesser (p < 0.01) than that of the D group. The conclusion is drawn that corticosterone has significant additional diabetogenic effects upon biochemical functions of liver mitochondria in the SZ-induced diabetic state which could occur through the hormone cellular receptors.
RESUMEN
El presente trabajo estudió el efecto del frío sobre el consumo del oxígeno (CO) y la actividad *-glicerofosfato deshidrogenasa (*-GPD) en mitocondria cardíaca de ratas hipotiroideas (hipo) tratadas con T3, T4 o T4 más Acido lopanoico (IOP). Se usaron ratas Wistar macho de 200g de peso hechas hipotiroideas con la administración de I. Los animales fueron inyectadoss s.c., en dosis divididas, por 10 días, con una de las siguientes sustancias: T3, 300 ng/100g peso/día; T4, 2 *g/100g peso/día o T4 más IOP, 5 mg/100g peso/día, por 72 hs. previas al experimento. Una mitad de cada grupo fue mantenida a 4ºC y el resto a 22ºC, por 24 hs., y logo decapitados. Se aislaron las mitocondrias de corazón por métodos de rutina. El CO se midió polarográficamente usando L-malato, L-glutamato y malonato como sustratos. La actividad mitocondrial *-GPD se medió por un método microcolorimétrico. Los resultados correspondientes a 16 o 20 ratas/grupo (4 o 5 "pooles" de 4 corazones cada uno) fueron los isguientes: En las ratas mantenidas a 22ºC el CO (en ng at. de oxíg./min/mg prot.; Estado 3) de las Hipo+T4 fue de 69 ñ 10; en el grupo tratado con T4+IOP fue de 75 ñ 11 y ... (AU)