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Abstract: We studied the effect of repeated exposure to dexamethasone (Dex) treatment on rat brain mitochondrial oxidative energy metabolism in developing rats at different postnatal ages, i.e. 2–5 week and in adults. The animals were injected with a dose of 2mg of Dex/kg body weight at around 7:00 a.m. for three alternative days prior to the day of sacrifice; the control group animals received saline vehicle. We measured rates of respiration with different substrates, viz. glutamate, pyruvate+malate, succinate and ascorbate+TMPD; the contents of individual cytochromes and the dehydrogenases and ATPase activities. Dex treatment, in general, stimulated the state 3 rates of respiration rates in young animals in age-dependent and substrate-specific manner except for the 3 week group, whereas in the adults there was substantial inhibition of the respiration. The pattern of dehydrogenases activities matched with respiration rates. Dex treatment also resulted in uncoupling of the second and third site of phosphorylation in 3-week-old animals and in the adults. The contents of cytochrome aa 3, b and ATPase activities decreased significantly after Dex treatment in all the age groups. The results thus emphasize that exposure to repeated Dex treatment can significantly influence the oxidative energy metabolism of brain mitochondria in young growing animals as well as in adults. [Copyright &y& Elsevier]

Abstract: Objectives: : Effects of treatment with dehydroepiandrosterone (DHEA) on oxidative energy metabolism in rat liver and brain mitochondria were examined. Design and methods: : Young adult rats were administered DHEA (0.1, 0.2, 1.0 or 2.0 mg/kg body weight) by subcutaneous route for 7 consecutive days. Results: : DHEA treatment resulted in general, in stimulation of state 3 respiration rates without having any uncoupling effect on ADP/O ratios. The stimulation of state 3 respiration rate for a given substrate was dose dependent in a tissue-specific manner. Parallel increases in the contents of cytochromes aa3 and b were also noted. DHEA treatment stimulated the glutamate dehydrogenase (GDH) and succinate DCIP reductase (SDR) activities. Under the treatment conditions, mitochondrial ATPase activity was also stimulated. Conclusions: : Treatment with DHEA significantly stimulated oxidative energy metabolism in liver and brain mitochondria. [Copyright &y& Elsevier]

Abstract: Effects of treatment with dehydroepiandrosterone (DHEA) (0.2 or 1.0mg/kg body weight for 7 days) on oxidative energy metabolism in cerebral mitochondria from developing and young adult rats were examined. Treatment with DHEA did not change the body weight of developing rats but resulted in increase in the brain weight in 5 week group. In young adult rats the body weight increased following treatment with 1.0mg DHEA. State 3 and state 4 respiration rates with all the substrates increased following DHEA treatment, the effect being more pronounced in the developing rats. State 4 respiration rates were stimulated to variable extents. Contents of cytochromes aa 3 and b increased following DHEA treatment and once again the effect was more pronounced in the developing rats. DHEA treatment marginally changed the content of cytochromes c + c 1. In the developing rats the ATPase activity and the levels of dehydrogenases increased significantly by DHEA treatment. Results of our studies have shown that treatment with exogenous DHEA accelerates the process of maturation of cerebral mitochondria thus emphasizing the role of DHEA in brain development in postnatal life. [Copyright &y& Elsevier]

Abstract: The content of the neurosteroids, dehydroepiandrosterone (DHEA) in the brain decreases with aging. Also the oxidative energy metabolism is known to decrease with aging. Hence we examined the effects of treatment with DHEA (0.2 or 1.0mg/kg body weight for 7 days) on oxidative energy metabolism in brain mitochondria from old and young adult rats. State 3 respiration rates in brain mitochondria from old animals were considerably lower than those in young adults. Treatment with DHEA stimulated state 3 and state 4 respiration rates in both the groups of the animals in a dose-dependent manner. In the old rats following DHEA treatment, the state 3 respiration rates became comparable to or increased beyond those of untreated young adults. In contrast to the old rats, stimulatory effect of DHEA treatment was of greater magnitude in the young adults. However, at higher dose (1.0mg) the effect declined. Cytochrome aa 3 content in the brain mitochondria from old rats was significantly low but the content of cytochrome b was unchanged while the content of cytochromes c + c 1 had increased. Treatment with DHEA increased the content of cytochrome aa 3 and b in old as well as in young adult animals. Higher dose of DHEA (1.0mg) had adverse effect on the content of cytochrome c + c 1 . DHEA treatment stimulated ATPase activity in a dose-dependent manner in young adult rats whereas in the old rats the effect on ATPase activity was marginal. Dehydrogenases activities were somewhat lower in the old rats. DHEA treatment stimulated mitochondrial dehydrogenases activities in both the groups. Results of our studies suggest that judicious use of DHEA treatment can improve oxidative energy metabolism parameters in brain mitochondria from young adult as well as old rats. [Copyright &y& Elsevier]

Dexamethasone— a potent synthetic glucocorticoid— has multiple therapeutic applications and, used in all age groups, as well as for antenatal and perinatal treatments. However, side-effects of dexamethasone treatment, including those on development, are becoming increasingly apparent. Since developmental processes are energy-dependent, we examined the effects of chronic dexamethasone treatment on oxidative energy metabolism in liver mitochondria from rats belonging to different developmental age groups. Dexamethasone treatment adversely affected the state 3 respiration rates in 2- and 3-week groups and in the adults with glutamate as the substrates, whereas for pyruvate + malate, the adverse effects were seen for the 3 week rats and the adult groups. Oxidation of succinate was severely impaired in all the age groups rats. For ascorbate + TMPD as the substrate, elevated respiration was noted for the 5-week group and the impaired oxidation was observed in adults. Dexamethasone treatment also resulted in site-specific uncoupling with the effect being seen predominantly in the 3- and 5-week and adult animals. The activity of dehydrogenases decreased in a manner comparable to the respiration rates. The mitochondrial cytochromes decreased in an age-dependent manner. The ATPase activity also decreased significantly. The results thus emphasize the adverse effects of dexamethasone treatment on mitochondrial energy metabolism especially in critical age groups. [ABSTRACT FROM AUTHOR]