Dehydroepiandrosterone protects low density lipoproteins against peroxidation by free radicals produced by γ-radiolysis of ethanol–water mixtures

Khalil, Abdelouahed; Lehoux, Jean‐Guy; Wagner, J. Richard; Lesur, Olivier; Cruz, Sandra Helena da; Dupont, Émilie; Jay‐Gerin, Jean‐Paul; Wallach, Jean; Fülöp, Tamás

doi:10.1016/s0021-9150(97)00194-9

Cited by 52 publications

(30 citation statements)

References 43 publications

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“…These wide-ranging activities cannot fully be explained by activation of the androgen or estrogen receptors. Published data support the hypothesis that DHEA acts to limit lipid peroxidation, in vivo as well as in vitro (17)(18)(19)(20)(21)(22)(23). Since many of the diseases on which DHEA has a beneficial effect have been related to repeated oxidative insult (24), the antioxidant properties of DHEA might be expected to explain its effects.…”

Section: Introductionmentioning

confidence: 63%

“…At these concentrations, DHEA has been reported to protect both bovine retinal capillary pericytes against glucose toxicity (23) and human low density lipoproteins (LDL) against peroxidation induced by g radiolysis of ethanol-water mixtures (22).…”

Section: Discussionmentioning

confidence: 99%

“…Alternatively, the addition of DHEA to the culture medium might modify the content of some antioxidant species, thus increasing the cell's defence against free radical damage. DHEA has recently been reported to protect human LDL against lipid peroxidation by regenerating the endogenous vitamin E of LDL (22). However, the content of vitamin E and other antioxidants has been reported to remain unchanged in tissue homogenates of DHEA-treated rats (21).…”

Section: Discussionmentioning

confidence: 99%

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Protective effect of dehydroepiandrosterone against lipid peroxidation in a human liver cell line

Gallo

Aragno

Gatto

et al. 1999

European Journal of Endocrinology

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Objective: Dehydroepiandrosterone (DHEA) is a widely studied steroid hormone with multi-functional properties. Reports suggest that some of the many activities of DHEA are due to its protective effect against lipid peroxidation. Nevertheless, the antioxidant properties of DHEA are still the subject of debate. The aim was to evaluate whether its two opposed effects on lipid peroxidation reported in the literature may be dependent on schedule and doses used. Methods: Chang liver cells, a line derived from normal human liver, were grown in media containing either no steroids (control) or DHEA at concentrations ranging from 0.1 mmol/l to 50 mmol/l. At specific times, cultures were halted and cells received a pro-oxidant stimulus (cumene (CuOOH) 0.5 mmol/l), at which time cell viability (by trypan blue staining and lactate dehydrogenase (LDH) release) and thiobarbituric acid reactive substances (TBARS) concentration (spectrophotometrical assay) were evaluated. Results: At concentrations ranging from 0.1 mmol/l to 1 mmol/l, DHEA protects Chang liver cells against lipid peroxidation and/or death induced by cumene. This effect disappears if the concentration is increased to 10 mmol/l; at higher concentrations (50 mmol/l) a pro-oxidant/cytotoxic effect of DHEA appears. Conclusions: DHEA exhibits two opposed effects on lipid peroxidation; depending on its concentration it acts either to limit or to induce oxidative stress. The threshold concentration at which the pro-oxidant activity of DHEA prevails is not far in excess of that having an antioxidant effect. Either effect of DHEA on lipid peroxidation is only evident after a 'lag-phase'.

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Section: Introductionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Protective effect of dehydroepiandrosterone against lipid peroxidation in a human liver cell line

Gallo

Aragno

Gatto

et al. 1999

European Journal of Endocrinology

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“…The ameliorative effect of a DHEA treatment against an oxidative imbalance have been suggested to be the key mechanism for its beneficial effect (Khalil et al, 1998;Aragno et al, 1999Aragno et al, , 2000aAragno et al, , 2000b. However, there is still some controversy regarding the ability of DHEA to protect against lipid peroxidation, probably because DHEA supplementation in rodents has been reported to increase the level of reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-dependent microsomal and mitochondrial lipid peroxidation, which is measured as the level of TBARS production in the rat liver and some extrahepatic tissues (Swierczynski et al, 1996a;Swierczynski et al, 1996b;Swierczynski et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that the administration of DHEA has many beneficial effect against many diseases (Green et al, 2001;Kuebler et al, 2001;Williams et al, 2002;Shilkaitis et al, 2005). The ameliorative effect of a DHEA against oxidative stress have been suggested as a key mechanism for its beneficial effect (Khalil et al, 1998;Khalil et al, 2000). Other studies have demonstrated that DHEA had antioxidant effect in various acute and chronic oxidative stress associated disorders (Aragno et al, 2000a;Brignardello et al, 2000;Aragno et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Pro-Oxidantive Effect of Dehydroepiandrosterone on Indomethacin-Induced Acute Gastritis in Rats

Kim¹,

Yim²,

Jeong³

et al. 2009

Biomolecules and Therapeutics

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-This study examined whether or not a pretreatment with dehydroepiandrosterone (DHEA) has an effect on indomethacin-induced gastric mucosal damage. The DHEA group, male Sprague-Dawley rats, was administrated with DHEA orally at a dose of 4 mg/day for one week before inducing gastritis with indomethacin (50 mg/kg, p.o.). Histological assay, lipid peroxidation assay, superoxide dismutase (SOD), glutathione peroxidase (GPx) and Catalase activities were determined. Interestingly, it was found that the DHEA pretreatment attenuated the gastric lesion area induced by indomethacin. Rather, the pretreatment with high dose of DHEA led to submucosal edema, leukocyte infiltration in submucosa and mucosal necrosis. The levels of MDA in the DHEA pretreatment were also higher than those in the rats given with vehicle pretreatment. This suggests that the DHEA pretreatment deteriorates severe inflammation in indomethacin-induced gastritis. DHEA supplementation significantly increased SOD activity in the gastric mucosa. However, the catalase and GPx activities were not altered by DHEA. The co-administration of DHEA with an indomethacin might not offer a protective effect against the acute gastritis induced by indomethacin.

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A unifying hypothesis of Alzheimer's disease. I. Ageing sets the stage

Heininger

1999

Hum. Psychopharmacol. Clin. Exp.

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In a series of ®ve papers, evidence from neurobiology, endocrinology and immunology is integrated into a holistic, coherent hypothesis accommodating genetic, medical and environmental risk factors into a cascade of pathophysiological events that leads to the clinical manifestation of Alzheimer's disease (AD). The perturbation of the calcium-energy-oxidative stress triangle emerges as pathophysiological leitmotif of ageing and AD. Cellular Ca 2 homeostasis and energy metabolism are closely interdependent. Ca 2 ions regulate the activity of a variety of ratelimiting enzymes of the tricarboxylic acid cycle and respiratory chain. Under physiological circumstances, the supply of energy according to demand is regulated by Ca 2 cycling across mitochondrial membranes. In certain pathological conditions, Ca 2 uncouples electron transfer and oxidative phosphorylation and increases the mitochondrial production of oxygen radicals which in tandem with Ca 2 precipitate the breakdown of mitochondrial function and structure. As most important risk factor, ageing sets the stage for the development of AD. The delicate regulation of the neuroendocrine network which physiologically modulates the Ca 2 -energy-redox homeostasis, deteriorates in ageing, compromising the hormonal balance between neurotrophic/protective and neuroaggressive factors. Thus, levels and/or signal transduction pathways of neurotrophic-factors such as neuropeptide Y, neurotrophins, DHEA/ DHEAS, gonadal hormones, melatonin, insulin, insulin-like growth factors, somatostatin, thyroid hormones, and substance P decay, paralleled by the compromise of the hypothalmic-pituitary-adrenal (HPA)-axis feedback inhibition leading to a hyperresponsiveness to stress and a loss of diurnal rhythm of secretion of neuroaggressive glucocorticoids. Both add up to disrupt Ca 2 and energy homeostasis, put the nerve cells under metabolic and oxidative stress and lead to a compromise of neuronal excitability, signal transduction processes and neuronal plasticity. Subject to the same endocrinological dysregulation, the ageing immune system exhibits a primitive response pattern with impairment of speci®c cellular and activation of unspeci®c humoral and microglial immune responses. Thus, the ageing-related concerted perturbation of the homeostatic control in the neuroendocrinoimmunological network creates phenomena which in many aspects are qualitatively similar to changes in AD and lay the foundations for the development of the disease.

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Dehydroepiandrosterone protects low density lipoproteins against peroxidation by free radicals produced by γ-radiolysis of ethanol–water mixtures

Cited by 52 publications

References 43 publications

Protective effect of dehydroepiandrosterone against lipid peroxidation in a human liver cell line

Protective effect of dehydroepiandrosterone against lipid peroxidation in a human liver cell line

Pro-Oxidantive Effect of Dehydroepiandrosterone on Indomethacin-Induced Acute Gastritis in Rats

A unifying hypothesis of Alzheimer's disease. I. Ageing sets the stage

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