DEHYDROEPIANDROSTERONE EFFECTS ON PLASMA ALPHA-TOCOPHEROL, METABOLIC AND HEMODYNAMIC PARAMETERS IN FRUCTOSE-OVERLOADED RATS

CARRANZA A.; GALLEANO M.; MAYER M.A.; FAYA I.; PEREDO H.A.; PUYO A.M.

Montevideo, Uruguay

Congreso; V Meeting of SFRBM-South America Group; 2007

SFRBM-South America Group

Fructose overload in rats induces insulin resistance, hypertension, dyslipidemia and also facilitates oxidative damage, which can disrupt the basal balance of vasoactive substances. The adrenal steroid dehydroepiandrosterone (DHEA) displays protective actions against oxidative stress. This study examines the effects of DHEA on blood pressure (BP), mesenteric vascular production of arachidonic acid-derived vasomodulators, triglyceridemia (TG) and plasma a-tocopherol (alpha-T). Male Sprague Dawley rats were divided in four groups: Control (C, tap water, n=6); Fructose (F, 10% w/v fructose solution, n=6); DHEA (D, DHEA sc, 15 mg/kg/d, n=6) and Fructose+DHEA (FD, both treatments, n=6) for 9 weeks. Indirect systolic BP was measured by the tall-cuff method, plasma TG by enzymatic assay and vascular release of prostanoids (PR) and plasma alpah-T by HPLC. Fructose increased BP (mmHg, F: 136±5 vs. C: 117±2, p< 0.01) and TG (mg/dl, F: 200 ± 26 vs. C: 101±14, p< 0.02), meanwhile DHEA reduced both parameters in FD (122 ± 1 vs. F, p<0,02; C: 106±13 vs. F, p< 0.01, respectively). Moreover, DHEA also decreased TG in D (D: 37±5 vs. C, p< 0.01). Fructose reduced vasodilator prostaglandins (PG) I2 and E2 (ng/mg tissue, F: 57±5 vs. C: 99±4, p<0,01; F:33±3 vs. C: 95±5, p<0,01). DHEA decreased vasoconstrictor PR, PGF2 a and thromboxane (Tx) A2 (FD: 48 ± 10 vs. F: 92±7, p< 0.05; FD: 25 ± 4 vs. F: 43±6, p< 0.05). DHEA markedly increased plasma alpha-T, corrected for TG, in D (mmol/mol TG, D: 62±10 vs. C: 23±3, p<0,01) and restored control values in FD (FD: 19 ± 5 vs. F: 12±2). In conclusion, DHEA improves plasma alpha-T in controls more markedly than in fructose-treated rats. In addition, DHEA lowers BP and triglyceridemia, and restores the balance between vasodilator and vasocontrictor PR, through the reduction in the release of the latter in the fructose group.