The effect of long-term DHEA treatment on glucose metabolism, hydrogen peroxide and thioredoxin levels in the skeletal muscle of diabetic rats

Jahn, Matheus Parmegiani; Jacob, Maria; Gomes, Luana Ferreira; Duarte, R.; Araújo, Alex Sander da Rosa; Ribeiro, Maria Flávia Marques; Kucharski, Luiz Carlos

doi:10.1016/j.jsbmb.2010.03.015

Cited by 16 publications

(7 citation statements)

References 60 publications

(73 reference statements)

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“…Sato et al ( 44 ) reported that GLUT-4 protein expression level was increased and the glucose metabolic signaling pathway was activated in skeletal muscle cells following DHEA-treatment. Jahn et al ( 45 ) demonstrated that muscle glucose oxidation was increased by 120% in diabetic Wistar rats treated with DHEA. Thus, the effect of DHEA on succinate dehydrogenase activity may be associated with its energy-wasting properties.…”

Section: Discussionmentioning

confidence: 99%

Dehydroepiandrosterone inhibits cell proliferation and improves viability by regulating S phase and mitochondrial permeability in primary rat Leydig cells

Liu

Wang

et al. 2016

Molecular Medicine Reports

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Dehydroepiandrosterone (DHEA) is widely used as a nutritional supplement and exhibits putative anti-aging properties. However, the molecular basis of the actions of DHEA, particularly on the biological characteristics of target cells, remain unclear. The aim of the current study was to investigate the effects of DHEA on cell viability, cell proliferation, cell cycle and mitochondrial function in primary rat Leydig cells. Adult Leydig cells were purified by Percoll gradient centrifugation, and cell proliferation was detected using a Click-iT® EdU Assay kit and cell cycle assessment performed using flow cytometry. Mitochondrial membrane potential was detected using JC-1 staining assay. The results of the current study demonstrate that DHEA decreased cell proliferation in a dose-dependent manner, whereas it improved cell viability in a time-dependent and dose-dependent manner. Flow cytometry analysis demonstrated that DHEA treatment increased the S phase cell population and decreased the G2/M cell population. Cyclin A and CDK2 mRNA levels were decreased in primary rat Leydig cells following DHEA treatment. DHEA treatment decreased the transmembrane electrical gradient in primary Leydig cells, whereas treatment significantly increased succinate dehydrogenase activity. These results indicated that DHEA inhibits primary rat Leydig cell proliferation by decreasing cyclin mRNA level, whereas it improves cells viability by modulating the permeability of the mitochondrial membrane and succinate dehydrogenase activity. These findings may demonstrate an important molecular mechanism by which DHEA activity is mediated.

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Section: Discussionmentioning

confidence: 99%

Dehydroepiandrosterone inhibits cell proliferation and improves viability by regulating S phase and mitochondrial permeability in primary rat Leydig cells

Liu

Wang

et al. 2016

Molecular Medicine Reports

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“…In addition, youngest rats present high levels of testosterone (400 pg/ml), declining significantly with aging, dropping more than 90% when the animal achieves 22 months of age [46]. Both DHEA and testosterone are known to increase the basal metabolism as demonstrated by the augmented cellular respiratory activity in young rats hepatocytes [47] and by the increase in glucose uptake in skeletal muscle in young rats [32]. Studies have also described that steroid hormones present a tissue-dependent effect in the rat muscle thus leading to a more pro-oxidant environment [48, 49].…”

Section: Discussionmentioning

confidence: 99%

“…Studies have also described that steroid hormones present a tissue-dependent effect in the rat muscle thus leading to a more pro-oxidant environment [48, 49]. Finally, treatment with DHEA caused a 2-fold decrease in thioredoxin antioxidant enzyme expression in skeletal muscle of young rats [32]. Taking all these evidence together, it is possible that the higher levels of H 2 O 2 observed in 3-months-old rats could be a consequence of a set of factors, including an augmented basal metabolism and a not-fully adapted antioxidant defense system favoring a pro-oxidant environment.…”

Section: Discussionmentioning

confidence: 99%

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DHEA Treatment Effects on Redox Environment in Skeletal Muscle of Young and Aged Healthy Rats

Jacob

Fernandes

Bonetto

et al. 2019

CAS

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Dehydroepiandrosterone (DHEA) is an important precursor of active steroid hormone, produced abundantly by the adrenal cortex with an age-dependent pattern. We investigated whether chronic DHEA administration impacts on redox status and on Akt protein activation in skeletal muscle during the aging process (3 and 24 month-old rats). Rats received one weekly dose/5 weeks of DHEA (10 mg/kg) or vehicle. Gastrocnemius muscle was removed to evaluate glutathione system, hydrogen peroxide, antioxidant enzymes, and expression of Akt kinase protein. In the 3-month-old rats DHEA induced an increase in hydrogen peroxide when compared both to its control (276%) and the 24-month-old DHEA group (485%). Moreover, in the 24-month-old rats DHEA caused an increase in GSSG (41 and 28%), a decrease in reduced-GSH (55 and 51%), and a more oxidized redox status (reduction in GSH/GSSG ratio, 47 and 65 %) when compared to 3-month-old DHEA and to 24-month-old control groups, respectively. Both older groups had increased G6PDH (2.7 fold) and GST (1.7 fold) activities when compared to younger groups, independently of any DHEA treatment. However, there was no modulation of Akt protein (phosphorylated/total isoform). The results show that chronic DHEA administration to 3 and 24-month-old rats may not present positive effects regarding the redox environment in skeletal muscle without modulation of pro-survival Akt kinase. Due to the large-scale self-administration of DHEA as an "anti-aging" dietary supplement, it is crucial to investigate its molecular mechanisms over oxidative stress-induced related diseases.

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“…Dehydroepiandrosterone (DHEA) is produced by the adrenal cortex and synthesized from pregnenolone and is further metabolized to androstenedione, testosterone, and estrogens (Aoki & Terauchi, 2018). Additionally, it can be synthesized in the central and peripheral nervous system (Jahn et al, 2010). Moreover, DHEA is regarded as a neurosteroid due to its impact on the brain's neurotransmitter receptors.…”

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confidence: 99%

Neurosteroid, Natural And Anabolic Steroids: Physiological, Immunological And Histopathological Study on Hyperlipidaemic Albino Rats

Khider,

Sofi,

Al-barwary

2023

UOD

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Neurosteroids are steroids that include endogenous steroids that the nervous system produces, and they function as neurotransmitters or neuromodulators. steroid hormones are chiefly produced in the adrenal glands and have a pivotal role in the regulation of many physiological actions in the body. An anabolic steroid, which is an artificial compound, has similar effects to testosterone. This study aimed at distinguishing between the roles of neurosteroid, natural steroid, and anabolic synthetic steroids by investigating the effects of some physiological, immunological, and histopathological on various target organs such as the Kidney, liver and spleen in hyperlipidemic rats. In order to achieve these aims, we randomly divided 50 male albino rats into five equal groups. The first group, which was fed on standard diet and injected subcutaneously with 0.5 ml of normal saline, was used as the control group, while the second group, which served as the hyperlipidemic control group was fed a high fat diet. The third group, hyperlipidemic rats, were orally administrated with DHEA (as a neurosteroid, 17.2mg/kg/day), the fourth group, hyperlipidemic rats, were subcutaneously injected with hydrocortisone (as a natural steroid, 26.1mg/kg/day). Finally, the fifth group of hyperlipidemic rats were intramuscularly injected with Sustanon (as an anabolic steroid, 66.9 mg/kg/week). The study has found that hyperlipidemic rats showed hematological parameters and interleukin IL-2 improvements with DHEA, fasting blood sugar and body weight with Sustanon and a lipid profile with both hydrocortisone and Sustanon, Renal function was almost deteriorated in all treated groups, and finally there were various alterations in the histopathological examination of kidney, liver and spleen. Finally, the study has come up with the following conclusions: DHEA administration can improve immunity and ameliorate tissue damage in the spleen. Hydrocortisone may improve the lipid profile, though it has negative effects on immunity and tissue health. Sustanon has positive effects on blood glucose and lipid profile; however, its effects on immunity are not clear enough.

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The effect of long-term DHEA treatment on glucose metabolism, hydrogen peroxide and thioredoxin levels in the skeletal muscle of diabetic rats

Cited by 16 publications

References 60 publications

Dehydroepiandrosterone inhibits cell proliferation and improves viability by regulating S phase and mitochondrial permeability in primary rat Leydig cells

Dehydroepiandrosterone inhibits cell proliferation and improves viability by regulating S phase and mitochondrial permeability in primary rat Leydig cells

DHEA Treatment Effects on Redox Environment in Skeletal Muscle of Young and Aged Healthy Rats

Neurosteroid, Natural And Anabolic Steroids: Physiological, Immunological And Histopathological Study on Hyperlipidaemic Albino Rats

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