Exogenous adiponectin with full Peroxisome proliferator-activated receptor agonists (pioglitazone) abrogates streptozotocin induced oxidative stress and vascular abnormalities in Spontaneously hypertensive rats.

Abstract

Background Oxidative stress, associates with metabolic and anthropometric perturbations, leads to reactive oxygen species production and decrease in plasma adiponectin concentration. We investigated pharmacodynamically the pathophysiological role and potential implication of exogenously administered adiponectin with full and partial peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonists on modulation of oxidative stress, metabolic dysregulation and antioxidant potential in streptozotocin induced Spontaneously hypertensive rats (SHR).Methods Group I (WKY) serve as normotensive control, whereas 42 male SHRs were randomized equally into 7 groups (n = 6), group II: SHR control, groups III: SHR diabetic control, group IV, V and VI treated with irbesartan (30 mg/kg), pioglitazone (10 mg/kg) and adiponectin (2.5 µg/kg), whereas, groups VII and VIII received co-treatments as irbesartan + adiponectin), (pioglitazone + adiponectin) respectively. Diabetes was induced using an intra-peritoneal injection of Streptozotocin (40 mg/kg). Plasma adiponectin, lipid contents, arterial stiffness with oxidative stress bio-markers were measured using an in-vitro and in-vivo analysis.Results Diabetic SHRs exhibited hyperglycaemia, hypertriglyceridemia, hypercholesterolemia, increased arterial stiffness with reduced plasma adiponectin and antioxidant enzymatic levels (P < 0.05). Diabetic SHRs pre-treated with pioglitazone and adiponectin separately exerted improvements in antioxidant enzyme activities, abrogated arterial stiffness, offset the increased production of reactive oxygen species and dyslipidaemic effects of STZ, except for blood pressure values which were more pronounced with irbesartan treated groups (all P < 0.05).Conclusions The combined treatment of exogenously administered adiponectin with full PPAR-γ agonist augmented the improvement in lipid contents and adiponectin concentration, restores arterial stiffness with antioxidant potential effects, indicating degree of synergism between adiponectin and full PPAR-γ agonists (pioglitazone).