Diosgenin, a steroidal saponin, prevents hypertension, cardiac remodeling and oxidative stress in adenine induced chronic renal failure rats

Abstract

Patients with chronic renal failure (CRF) are at a high risk of developing cardiovascular diseases. The aim of the present study was to evaluate the effect of diosgenin on blood pressure, cardiac remodeling, contractile function and gene expression program in the context of oxidative stress in CRF rats. CRF was induced in rats by feeding them with 0.75% adenine-containing diet, and diosgenin was given orally everyday at the dose of 10, 20 and 40 mg kg⁻¹ body weight of animal. The effect of diosgenin on systolic blood pressure (SBP), activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), angiotensin converting enzyme (ACE) activity and lipid peroxidation level in heart were evaluated. Cardiac function (dp/dt) and percentage rate pressure product (%RPP) recovery after ischemia/reperfusion (I/R) were evaluated by Langendorff isolated heart system, and gene expression levels were assessed by real-time PCR. Fibrotic remodeling of heart was assessed by histopathologic analyses. The outcome of this study demonstrated that a dose dependent treatment with diosgenin reduces hypertension in CRF animals, and a 40 mg kg⁻¹ dosage exhibited more pronounced effect on the blood pressure. Diosgenin enhances the antioxidant level, attenuates ACE activity, lipid peroxidation level and cardiac fibrosis. Ventricular function and %RPP recovery after I/R were also improved by the diosgenin treatment. CRF induced expression of transforming growth factor-β (TGF-β) and β-myosin heavy chain (β-MHC) were also suppressed by diosgenin. Taken together, these results suggest that diosgenin have enough potential to attenuate cardiac remodeling by reducing blood pressure and oxidative stress in the heart of CRF rats.