Apocynin influence on oxidative stress and cardiac remodeling of spontaneously hypertensive rats with diabetes mellitus

Abstract

PurposeAlthough increased oxidative stress is a major component of diabetic hypertensive cardiomyopathy, research into the effects of antioxidants on cardiac remodeling remains scarce. The actions of antioxidant apocynin include inhibiting reactive oxygen species (ROS) generation by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and ROS scavenging. We evaluated the effects of apocynin on cardiac remodeling in spontaneously hypertensive rats (SHR) with diabetes mellitus (DM).MethodsMale SHR were divided into four groups: control (SHR, n = 16); SHR treated with apocynin (SHR-APO; 16 mg/kg/day, added to drinking water; n = 16); diabetic SHR (SHR-DM, n = 13); and SHR-DM treated with apocynin (SHR-DM-APO, n = 14), for eight weeks. DM was induced by streptozotocin (40 mg/kg, single dose). Statistical analyzes: ANOVA and Tukey or Mann–Whitney.ResultsEchocardiogram in diabetic groups showed higher left ventricular and left atrium diameters indexed for body weight, and higher isovolumetric relaxation time than normoglycemic rats; systolic function did not differ between groups. Isolated papillary muscle showed impaired contractile and relaxation function in diabetic groups. Developed tension was lower in SHR-APO than SHR. Myocardial hydroxyproline concentration was higher in SHR-DM than SHR, interstitial collagen fraction was higher in SHR-DM-APO than SHR-APO, and type III collagen protein expression was lower in SHR-DM and SHR-DM-APO than their controls. Type I collagen and lysyl oxidase expression did not differ between groups. Apocynin did not change collagen tissue. Myocardial lipid hydroperoxide concentration was higher in SHR-DM than SHR and SHR-DM-APO. Glutathione peroxidase activity was lower and catalase higher in SHR-DM than SHR. Apocynin attenuated antioxidant enzyme activity changes in SHR-DM-APO. Advanced glycation end-products and NADPH oxidase activity did not differ between groups.ConclusionApocynin reduces oxidative stress independently of NADPH oxidase activity and does not change ventricular or myocardial function in spontaneously hypertensive rats with diabetes mellitus. The apocynin-induced myocardial functional impairment in SHR shows that apocynin actions need to be clarified during sustained chronic pressure overload.

Temporal Measures in Cardiac Structure and Function During the Development of Obesity Induced by Different Types of Western Diet in a Rat Model

“…The first echocardiographic analysis was performed at the 17th week of dietary treatment and evaluated every 2 months until the 41st week, totaling four moments of study (17,25,33, and 41 weeks). The analysis was performed using commercially available echocardiography (General Electric Medical Systems, Vivid S6, Tirat Carmel, Israel) equipped with a 5-11.5 MHz multi-frequency transducer, as previously described [22]. Rats were anesthetized by intraperitoneal injection of a mixture of ketamine (50 mg/kg) and xylazine (1 mg/kg).…”

Role of Advanced Glycation End Products in the Progression of Diabetes Mellitus

“…Oxidative Stress and AGEs: AGEs, as the oxidative products, can induce OS, promote cell apoptosis, and fi nally induce both micro-and macro-vascular disease in diabetic patients [26,[54][55][56][57]. Direct cellular challenge with AGEs has been shown to cause OS in various cell types [58][59][60]. It is found that Schiffbase products and Amadori products themselves cause ROS production [61], while Nitric Oxide (NO) donors can scavenge free radicals and inhibit AGEs formation [62].…”

Green tea (Cammellia sinensis) attenuates ventricular remodeling after experimental myocardial infarction

“…Rats were anesthetized by intramuscular injection of a mixture of ketamine (50 mg/kg) and xylazine (0.5 mg/kg). The cardiac structures were measured according to previous methods in an infarcted rat model [16][17][18]. Left ventricle end-diastolic dimension (LVDD), left ventricle end-systolic dimension (LVSD) and posterior wall thickness (LVWT) were measured at the maximal diastolic dimension, taken at the maximal anterior motion of the posterior wall.…”

“…LV systolic function was assessed by the following parameters: fractional shortening (FS) [(LVDD − LVSD) / LVDD] × 100, fractional area change (FAC) (DA − SA / DA × 100) and tissue Doppler imaging (TDI) of mitral annulus systolic velocity (S′). Diastolic function was evaluated by E wave deceleration time (EDT) assessed by pulsed wave Doppler and early diastolic mitral inflow velocities (E) and TDI of early mitral annulus diastolic velocity (E′) ratio (E/E′) [18].…”