Hypoxia and dehydroepiandrosterone in old age: a mouse survival study

Debonneuil, Edouard; Quillard, J; Baulieu, Étienne-Émile

doi:10.1186/1465-9921-7-144

Cited by 24 publications

(18 citation statements)

References 42 publications

(53 reference statements)

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“…44 Circulating DHEA concentration in humans ranges from 10 j9 to 10 j7 M, and oral DHEA administration at 25 to 50 mg/kg results in similar circulating concentrations. 15,45,46 Thus, a dose of 30 mg kg j1 day j1 used in the present study predicts that plasma concentrations should be greater than 10 j7 M, 47,48 relatively higher than circulating levels seen in humans. Thus, we speculate that DHEA treatment at that dose is sufficient to promote pharmacological activity.…”

Section: Discussionmentioning

confidence: 94%

Distinct cardioprotective effects of 17β-estradiol and dehydroepiandrosterone on pressure overload–induced hypertrophy in ovariectomized female rats

et al. 2011

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Section: Discussionmentioning

confidence: 94%

Distinct cardioprotective effects of 17β-estradiol and dehydroepiandrosterone on pressure overload–induced hypertrophy in ovariectomized female rats

et al. 2011

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“…In the present study, oral administration of DHEA at doses 15 and 30 mg/kg/day expecting to induce plasma concentration of DHEA range from 10 27 to 10 26 mol/L. 48,49 During vehicle or DHEA administration the body weight (BW) and food intake of the rats were observed everyday.…”

Section: Dhea Administrationmentioning

confidence: 99%

Stimulation of Sigma-1 receptor by dehydroepiandrosterone ameliorates hypertension-induced kidney hypertrophy in ovariectomized rats

Bhuiyan

Fukunaga

2010

Exp Biol Med (Maywood)

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The incidence of chronic renal disease in women increases with aging, especially after menopause, suggesting that loss of sex hormones contributes to the development and progression of renal diseases. Recent studies revealed that decreased dehydroepiandrosterone (DHEA) levels are associated with endothelial dysfunction, renal injury and increased cardiovascular mortality in postmenopausal women. We here investigate the role of DHEA, also known as Sigma-1 receptor (Sigma-1R) agonist, on kidney injury induced by pressure overload (PO) after ovariectomy (OVX) and defined mechanisms underlying its protective action. Wistar rats subjected to bilateral OVX were further treated with abdominal aortic stenosis between the right and left renal arteries. DHEA (15 and 30 mg/kg) was administered orally once a day for 14 days starting from two weeks after aortic banding. Time course study indicated that the right kidney (RK) weight-to-body weight (BW) ratio increases time-dependently from one to four weeks along with increased mean arterial blood pressure (MABP) after banding in the abdominal aorta with no change in the left kidney (LK) weight-to-BW ratio. Similarly, we found significant time-dependent decrease in Sigma-1R expression in the RK with no changes in the LK. Administration of the Sigma-1R agonist, DHEA, significantly inhibited hypertension-induced increases in the RKW-to-BW ratio and increased expression of Sigma-1R in the RK. DHEA also attenuated PO-induced disturbance of heart rate and MABP. DHEA administration significantly restored PO-induced impaired endothelial nitric oxide synthase (eNOS) activity with concomitant increased phosphorylation of eNOS (Ser1179) and Akt activity with increased phosphorylation at Ser 473 and at Thr 308 in the RK. We here documented, for the first time, the potential role of Sigma-1R to protect the kidney from PO-induced injury in ovariectomized rats. DHEA administration protects hypertension-induced kidney injury via upregulation of Sigma-1R and stimulation of Akt-eNOS signaling in ovariectomized rats.

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“…Low oxygen tension lengthened the lifespan of human diploid fibroblasts (Chen et al, 1995), but reduced the lifespan of human CD4 and T cell clones (Duggan et al, 2004). Mice showed a lifespan reduction in hypoxia and detrimental physiological changes such as severe weight loss, trembling and polycythemia (Debonneuil et al, 2006). Conversely, low oxygen tensions have been shown to lengthen the lifespan of C. elegans (Honda and Honda, 2002).…”

Section: Introductionmentioning

confidence: 99%

Lifespan and oxidative stress show a non-linear response to atmospheric oxygen inDrosophila

Rascón

Harrison

2010

Journal of Experimental Biology

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SUMMARYOxygen provides the substrate for most ATP production, but also serves as a source of reactive oxygen species (ROS), which can induce cumulative macromolecular oxidative damage and cause aging. Pure oxygen atmospheres (100kPa) are known to strongly reduce invertebrate lifespan and induce aging-related physiological changes. However, the nature of the relationship between atmospheric oxygen, oxidative stress, and lifespan across a range of oxygen levels is poorly known. Developmental responses are likely to play a strong role, as prior research has shown strong effects of rearing oxygen level on growth, size and respiratory system morphology. In this study, we examined (1) the effect of oxygen on adult longevity and (2) the effect of the oxygen concentration experienced by larvae on adult lifespan by rearing Drosophila melanogaster in three oxygen atmospheres throughout larval development (10, 21 and 40kPa), then measuring the lifespan of adults in five oxygen tensions (2, 10, 21, 40, 100kPa). We also assessed the rate of protein carbonyl production for flies kept at 2, 10, 21, 40 and 100kPa as adults (all larvae reared in normoxia). The rearing of juveniles in varying oxygen treatments affected lifespan in a complex manner, and the effect of different oxygen tensions on adult lifespan was non-linear, with reduced longevity and heightened oxidative stress at extreme high and low atmospheric oxygen levels. Moderate hypoxia (10kPa) extended maximum, but not mean lifespan.

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Hypoxia and dehydroepiandrosterone in old age: a mouse survival study

Cited by 24 publications

References 42 publications

Distinct cardioprotective effects of 17β-estradiol and dehydroepiandrosterone on pressure overload–induced hypertrophy in ovariectomized female rats

Distinct cardioprotective effects of 17β-estradiol and dehydroepiandrosterone on pressure overload–induced hypertrophy in ovariectomized female rats

Stimulation of Sigma-1 receptor by dehydroepiandrosterone ameliorates hypertension-induced kidney hypertrophy in ovariectomized rats

Lifespan and oxidative stress show a non-linear response to atmospheric oxygen inDrosophila

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