Abstract
Oxidative stress, which is associated 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). Group I (WKY) serves as the normotensive control, whereas 42 male SHRs were randomized equally into 7 groups (n = 6); group II serves as the SHR control, group III serves as the SHR diabetic control, and groups IV, V, and VI are treated with irbesartan (30 mg/kg), pioglitazone (10 mg/kg), and adiponectin (2.5 μg/kg), whereas groups VII and VIII received cotreatments as irbesartan+adiponectin and pioglitazone+adiponectin, respectively. Diabetes was induced using an intraperitoneal injection of streptozotocin (40 mg/kg). Plasma adiponectin, lipid contents, and arterial stiffness with oxidative stress biomarkers were measured using an in vitro and in vivo analysis. Diabetic SHRs exhibited hyperglycemia, hypertriglyceridemia, hypercholesterolemia, and increased arterial stiffness with reduced plasma adiponectin and antioxidant enzymatic levels (P < 0.05). Diabetic SHRs pretreated with pioglitazone and adiponectin separately exerted improvements in antioxidant enzyme activities, abrogated arterial stiffness, and offset the increased production of reactive oxygen species and dyslipidemic effects of STZ, whereas the blood pressure values were significantly reduced in the irbesartan-treated groups (all P < 0.05). The combined treatment of exogenously administered adiponectin with full PPAR-γ agonist augmented the improvement in lipid contents and adiponectin concentration and restored arterial stiffness with antioxidant potential effects, indicating the degree of synergism between adiponectin and full PPAR-γ agonists (pioglitazone).
Highlights
Diabetes mellitus (DM) and hypertension (HTN) are being considered foremost public health and medical issues; their coexistence has received greater attention because of rising epidemic globally as common chronic diseases, which associate mainly with micro- and macrocardiovascular complications [1], accelerating hyperglycemic issues in diabetic individuals [2]
Forty-two (42) spontaneously hypertensive rats (SHR) were divided into 7 groups, whereas thirty-six (36) SHRs (6 groups) received STZ and were treated as per experimental protocol and six (6) SHRs served as the control (SHR+CNT) group
There was no significant difference in fluid intake in the Wistar Kyoto rats (WKY)+CNT group (P > 0:05), but it remained significantly lower in the SHR+CNT group as compared to the WKY control group on all 4 days of observation (P < 0:05)
Summary
Diabetes mellitus (DM) and hypertension (HTN) are being considered foremost public health and medical issues; their coexistence has received greater attention because of rising epidemic globally as common chronic diseases, which associate mainly with micro- and macrocardiovascular complications [1], accelerating hyperglycemic issues in diabetic individuals [2]. Previous studies signify the role of hyperglycemia leading to oxidative stress (OS) with endothelial dysfunction in blood vessels of type 1 diabetic patients [3]. The concepts of oxidative stress and endothelial dysfunction have gained interest in recent years as contributing factors in the pathogenesis of hypertension and diabetes. PPAR Research oxidative stress (OS) and reactive oxygen species (ROS) [6]. Oxidative stress and derivatives of reactive oxygen metabolites significantly aggravate in diabetic states [1, 3], essential hypertension [7], and hyperlipidemia disorders [8], whereas this pathogenesis relates directly to the biological antioxidant capacity of the body [9]. Recent studies have shown that oxidative stress negatively regulates the adiponectin gene expression [10]; its concentration in plasma impacts oxidative stress [2, 11]
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