Improving Effects Obtained by the Ovariectomy or Treatment with Tamoxifen of Female Diabetic Rats over the Function and Enzyme Activities of Liver Mitochondria

Abstract

In the present work we studied, in female chronic diabetic rats the effect of either the parenteral administration of tamoxifen (TAM) (500 micrograms.kg-1.day-1) for 15 days or the ovariectomy upon the respiration and oscillatory behaviour of intact mitochondria and the activities of 3-hydroxybutyrate dehydrogenase (HBD) and cytochrome c oxidase (Cox) of disrupted liver mitochondria. The treatment with TAM as well as the ovariectomy of diabetic animals significantly increased the respiratory control (RC) and the state 3 (S3) of respiration of intact liver mitochondria with the three substrates assayed (3-hydroxybutyrate, malate-glutamate and succinate). Both treatments also lowered significantly the damped factors of the oscillatory variation of liver intact mitochondria of diabetic rats. Moreover, the two above-mentioned treatments restored the activities of HBD and Cox of liver disrupted mitochondria to normal values. The effect of estrogens at level of its receptors in the modulation of liver mitochondrial function and liver HBD and Cox activities in chronic diabetes is discussed.

Palladium-α-lipoic acid complex attenuates alloxan-induced hyperglycemia and enhances the declined blood antioxidant status in diabetic rats

“…Significant biochemical and molecular changes occur in mitochondria of the liver, kidneys, and brain with experimentally‐induced diabetes. Mitochondria are one of the primary targets of ROS generated during the oxidative stress induced in diabetes, 28 which in turn damages mitochondrial DNA. The depletion of the intracellular concentration of nicotinamide adenine dinucleotide‐oxidized (NAD + ), electron transport, and ATP formation can be ascribed to the activation of the nuclear enzyme poly(ADP‐ribose) polymerase, which is stimulated by the ROS‐induced DNA damage 29,30 .…”

An overview of Argentine contributions to diabetes research in the decade of the 1990s

“…Oophorectomy of diabetic rats significantly improved all the parameters measured to assess mitochondrial function, while administration of 17‐ β estradiol to these rats restored the diabetic alterations of the mitochondrial function158. Furthermore, treatment of intact diabetic animals with tamoxifen (an estrogen antagonist) reproduced the ameliorating effect of oophorectomy upon the impaired liver mitochondrial function159–163. Similarly, bilateral adrenalectomy of diabetic rats or their treatment with a specific glucocorticoid antagonist (RU 38486) produced significant improvement of mitochondrial function.…”

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“…During the oestrus cycle in rats, E2 decreased complex IV activity in brown adipose tissue, which suggests a role for E2 in the modulation of oxidative capacity [55]. The ER ligand tamoxifen was reported to restore complex IV activity to normal levels in disrupted rat liver mitochondria [56]. In rat liver mitochondria, tamoxifen was demonstrated to have a biphasic effect on complex IV in which a low concentration of 10–15 μM increased enzyme activity while a higher concentration of 50 μM inhibited activity by 50% [30].…”