Dehydroepiandrosterone (DHEA) is a neurosteroid produced in the brain, but its levels decline significantly with age, increasing neuronal vulnerability to neuromodulatory changes. This study aimed to evaluate whether DHEA supplementation could restore age-related alterations in renal metabolism. Specifically, the study examined the impact of DHEA on antioxidant enzyme activity, renal glucose homeostasis, serum creatinine levels, urine output, urine microscopy, osteopontin expression, serum lipid profile, glomerular filtration rate, and overall renal function in male rats across three age groups: young (4 months), adult (14 months), and old (24 months).

Aged male rats (14 and 24 months old) received daily subcutaneous injections of DHEA (30 mg/kg body weight) for one month. Following the treatment period, all animals were sacrificed, and kidney microsomes were isolated for further biochemical analysis. Key parameters measured included non-enzymatic glutathione (GSH) levels, enzymatic antioxidants such as superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT), hepatic glucose homeostasis, lipogenic enzyme activity, lipid metabolism, and markers of renal function, including serum creatinine, urine output, and glomerular filtration rate.

Aging was associated with a significant reduction in antioxidant enzyme activity, glomerular filtration rate, and urine output, while hepatic glucose homeostasis, osteopontin expression, lipogenic enzyme activity, lipid profile, and serum creatinine levels showed a marked increase. Treatment with DHEA effectively mitigated these age-related changes, with the DHEA group demonstrating the most substantial improvements in renal function, bringing these parameters closer to youthful levels.

The findings suggest that DHEA supplementation plays a protective role in renal function, potentially counteracting age-related renal decline. This highlights its potential as a therapeutic intervention for reducing the risk of chronic kidney diseases associated with aging.