Dehydroepiandrosterone prevents lipid peroxidation and cell growth inhibition induced by high glucose concentration in cultured rat mesangial cells

The oxidative stress induced by high glucose concentration contributes to t issue damage associated with diabetes, including renal injury. Dehydroepian drosterone (DHEA), the major secretory product of the human adrenal gland, has been shown tu possess a multi-targeted antioxidant activity which is al so effective against lipid peroxidation induced by high glucose. In this st udy we evaluated the effect of DHEA on the growth impairment which high glu cose concentration induces in cultured rat mesangial cells. Primary culture s of rat mesangial cells were grown for 10 days in media containing either normal (i.e. 5.6 mmol/l) or high (i.e. 30 mmol/l) concentrations of glucose , without or with DHA at different concentrations. The impairment of cell g rowth induced by high glucose was reversed by 100 mol/l and 500 nmol/l DHEA , which had no effect on mesangial cells cultured in media containing gluco se at the normal physiological concentration (5.6 nmol/l). In high-glucose cultured mesangial cells, DHEA also attenuated the lipid peroxidation, as m easured by thiobarbituric acid reactive substances (TBARS) generation and 4 -hydroxynonenal (HNE) concentration, and prescribed the cellular content of reduced glutathione as well as the membrane Na+/K+ ATPase activity. The da ta further support the protective effect of DHEA against oxidative damage i nduced by high glucose concentrations, and bring into focus its possible ef fectiveness in preventing chronic complications of diabetes,