Therapeutic effects of tamoxifen on metabolic parameters and cytokines modulation in rat model of postmenopausal diabetic cardiovascular dysfunction: Role of classic estrogen receptors

Abstract

In postmenopausal women, the risk of diabetic cardiovascular disease drastically increases compared with that of premenopausal women. In the present study we surveyed the effects of Tamoxifen (TAM) and 17-β-estradiol (E2) on diabetic cardiovascular dysfunction. Female wistar rats were divided into six groups: sham-control, Diabetes, Ovariectomized (OVX) + Diabetes, OVX + Diabetes + Vehicle, OVX + Diabetes + E2, OVX + Diabetes + TAM. Type 2 diabetes was induced by High Fat Diet and low doses of STZ. E2 and TAM were administrated every four days for four weeks. Results show that, TAM or E2 reduces cardiac weight, atherogenic and cardiac risk indices. Mean arterial blood pressure (MABP) increased in diabetes group, while TAM and E2 prevented MABP increment. Also, fasting blood glucose was decreased by TAM and E2. Significant decrement in the level of IL-10 was observed in diabetes group and this effect was abolished by TAM and E2. Also, treatment with TAM and E2 resulted in improved inflammatory balance in favor of anti-inflammation. Although diabetes resulted in, increment of TC and LDL, TAM and E2 reduced lipids profile. Furthermore, treatment with TAM prevented the reduction of estrogen receptors (ERs) α and β protein levels, but its effect on the ERβ protein level was higher. Our results indicated that TAM protects against diabetic cardiovascular dysfunction and is a good candidate for E2 substitution.