Toxic Impact of Anabolic Androgenic Steroids in Primary Rat Cortical Cell Cultures

Zelleroth, Sofia; Nylander, Erik; Nyberg, Fred; Grönbladh, Alfhild; Hallberg, Mathias

doi:10.1016/j.neuroscience.2018.11.035

Cited by 25 publications

(15 citation statements)

References 54 publications

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“…The finding of more evident brain aging associated with long term use of AAS, is consistent with in vitro studies suggesting that various sorts of AAS might have neurotoxic effects (19)(20)(21)(22)(23)(24), and recent findings of impaired cognitive performance (12,32,33), smaller brain volumes (30), and metabolites abnormalities ( 29), associated with long-term AAS use. The finding of older appearing brains in AASdependent compared to non-dependent users is consistent with a mega-analyses pooling data from 23 cohorts suggesting that dependency shares a common neural substrate across a range of substances, indicating smaller brain volumes and thinner cortex in dependent relative to nondependent individuals (67).…”

Section: Aas Use Associated With Apparent Brain Agingsupporting

confidence: 83%

“…There is growing evidence suggesting that high-dose long-term exposure to AAS have harmful effects on the brain. Cell culture studies have shown neurotoxic effects of various sorts of AAS (19)(20)(21)(22)(23)(24), in particular in response to high dosages mimicking those taken by body builders and recreational athletes (23,24). Contrary, neuroprotective effects of physiological doses of testosterone have been observed (25,26).…”

Section: Introductionmentioning

confidence: 99%

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Long-term anabolic androgenic steroid use is associated with deviant brain aging

Bjørnebekk

Kaufmann

Hauger

et al. 2020

Preprint

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Background High-dose long-term use of anabolic-androgenic steroids (AAS) may bring a range of health consequences, including brain and cognitive abnormalities. We performed age prediction based on brain scans to test whether prolonged AAS use is associated with accentuated brain aging. Methods T1-weighted brain MRI data were obtained from male weightlifters with a history of prolonged (n=133) or no (n=105) AAS use. We trained machine learning models on combinations of regional brain volumes, cortical thickness and surface area in an independent training set of 1838 healthy males aged 18-92 years and predicted brain age for each participant in our study. We used linear models to compare the gap between chronological age and predicted brain age (the brain age gap, BAG) between the two groups, and, in a subsample with longitudinal data (mean interval 3.5 years), tested for group differences in the change rate of BAG. Moreover, we tested for associations between apparent brain aging and AAS use duration, administration pattern and dependence. Results AAS users had higher BAG compared to weightlifting controls with strongest effects for frontal and insular regions. Higher BAG was associated with current AAS use, dependency, and longer history of AAS use. Group differences in BAG could not be explained by substance use, general cognitive abilities or depression. Longitudinal data revealed no group difference in the rate of BAG change. Conclusions The findings suggest that long-term high dose AAS use may have adverse effects on brain aging, potentially linked to current and exaggerated use of AAS.

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Section: Aas Use Associated With Apparent Brain Agingsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Long-term anabolic androgenic steroid use is associated with deviant brain aging

Bjørnebekk

Kaufmann

Hauger

et al. 2020

Preprint

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“…At the same time, our data may be relevant to the experimental studies of steroid hormones action in vivo, studies with whole animals or (and particularly so) with cell cultures. Concentration of the hormones employed in such studies often reach a submillimolar or even millimolar range [ 29 , 30 , 31 , 32 , 33 ]. For example, in the paper of D’Ascenzo et al [ 29 ], the following IC 50% values are cited for inhibition of cell growth by anabolic steroides: testosterone, 100 µM; androstenedione, 375 µM; nandrolone, 9 µM; norandrostenedione, 500 µM; norandrostenediol, 6 mM.…”

Section: Discussionmentioning

confidence: 99%

Interaction of Cytochrome C Oxidase with Steroid Hormones

Oleynikov

Azarkina

Vygodina

et al. 2020

Cells

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Estradiol, testosterone and other steroid hormones inhibit cytochrome c oxidase (CcO) purified from bovine heart. The inhibition is strongly dependent on concentration of dodecyl-maltoside (DM) in the assay. The plots of Ki vs [DM] are linear for both estradiol and testosterone which may indicate an 1:1 stoichiometry competition between the hormones and the detergent. Binding of estradiol, but not of testosterone, brings about spectral shift of the oxidized CcO consistent with an effect on heme a33+. We presume that the hormones bind to CcO at the bile acid binding site described by Ferguson-Miller and collaborators. Estradiol is shown to inhibit intraprotein electron transfer between hemes a and a3. Notably, neither estradiol nor testosterone suppresses the peroxidase activity of CcO. Such a specific mode of action indicates that inhibition of CcO activity by the hormones is associated with impairing proton transfer via the K-proton channel.

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“…However, abuse of AASs is believed to be widespread among bodybuilders because supratherapeutic doses of synthetic AASs enhance athletic performance and physical appearance (Kanayama et al 2010). Such high doses of AASs entail behavioral changes, cardiovascular incidents, and metabolic disorders (Grönbladh et al 2013;Kanayama et al 2008;Pospíšilová et al 2012;Steensland et al 2005;van Amsterdam et al 2010;Zelleroth et al 2019). Hence, the effects of supratherapeutic doses of AASs are a source of public concern.…”

Section: Introductionmentioning

confidence: 99%

Anabolic androgenic steroids exert a selective remodeling of the plasma lipidome that mirrors the decrease of the de novo lipogenesis in the liver

et al. 2020

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Introduction The abuse of anabolic androgenic steroids (AASs) is a source of public concern because of their adverse effects. Supratherapeutic doses of AASs are known to be hepatotoxic and regulate the lipoproteins in plasma by modifying the metabolism of lipids in the liver, which is associated with metabolic diseases. However, the effect of AASs on the profile of lipids in plasma is unknown. Objectives To describe the changes in the plasma lipidome exerted by AASs and to discuss these changes in the light of previous research about AASs and de novo lipogenesis in the liver. Methods We treated male Wistar rats with supratherapeutic doses of nandrolone decanoate and testosterone undecanoate. Subsequently, we isolated the blood plasma and performed lipidomics analysis by liquid chromatography-high resolution mass spectrometry. Results Lipid profiling revealed a decrease of sphingolipids and glycerolipids with palmitic, palmitoleic, stearic, and oleic acids. In addition, lipid profiling revealed an increase in free fatty acids and glycerophospholipids with odd-numbered chain fatty acids and/or arachidonic acid. Conclusion The lipid profile presented herein reports the imprint of AASs on the plasma lipidome, which mirrors the downregulation of de novo lipogenesis in the liver. In a broader perspective, this profile will help to understand the influence of androgens on the lipid metabolism in future studies of diseases with dysregulated lipogenesis (e.g. type 2 diabetes, fatty liver disease, and hepatocellular carcinoma).

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Toxic Impact of Anabolic Androgenic Steroids in Primary Rat Cortical Cell Cultures

Cited by 25 publications

References 54 publications

Long-term anabolic androgenic steroid use is associated with deviant brain aging

Long-term anabolic androgenic steroid use is associated with deviant brain aging

Interaction of Cytochrome C Oxidase with Steroid Hormones

Anabolic androgenic steroids exert a selective remodeling of the plasma lipidome that mirrors the decrease of the de novo lipogenesis in the liver

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