Background: Dehydroepiandrosterone (DHEA) is an important precursor of active steroid
hormone, produced abundantly by the adrenal cortex with an age-dependent pattern.
Objective: 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 months-old rats).
Methods: 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.
Results: In the 3-months-old rats DHEA induced an increase in hydrogen peroxide when compared
both to its control (276%) and the 24-months-old DHEA group (485%). Moreover, in the 24-
months-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-months-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
Conclusion: The results show that chronic DHEA administration to 3 and 24-months-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 stressinduced