Influence of apocynin on cardiac remodeling in rats with streptozotocin-induced diabetes mellitus

Abstract

BackgroundIncreased reactive oxygen species (ROS) generation in diabetes mellitus (DM) is an important mechanism leading to diabetic cardiomyopathy. Apocynin, a drug isolated from the herb Picrorhiza kurroa, is considered an antioxidant agent by inhibiting NADPH oxidase activity and improving ROS scavenging. This study analyzed the influence of apocynin on cardiac remodeling in diabetic rats.MethodsSix-month-old male Wistar rats were assigned into 4 groups: control (CTL, n = 15), control + apocynin (CTL + APO, n = 20), diabetes (DM, n = 20), and diabetes + apocynin (DM + APO, n = 20). DM was induced by streptozotocin. Seven days later, apocynin (16 mg/kg/day) or vehicle was initiated and maintained for 8 weeks. Left ventricular (LV) histological sections were used to analyze interstitial collagen fraction. NADPH oxidase activity was evaluated in LV samples. Comparisons between groups were performed by ANOVA for a 2 × 2 factorial design followed by the Bonferroni post hoc test.ResultsBody weight (BW) was lower and glycemia higher in diabetic animals. Echocardiogram showed increased left atrial diameter, LV diastolic diameter, and LV mass indexed by BW in both diabetic groups; apocynin did not affect these indices. LV systolic function was impaired in DM groups and unchanged by apocynin. Isovolumic relaxation time was increased in DM groups; transmitral E/A ratio was higher in DM + APO compared to DM. Myocardial functional evaluation through papillary muscle preparations showed impaired contractile and relaxation function in both DM groups at baseline conditions. After positive inotropic stimulation, developed tension (DT) was lower in DM than CTL. In DM + APO, DT had values between those in DM and CTL + APO and did not significantly differ from either group. Myocardial interstitial collagen fraction was higher in DM than CTL and did not differ between DM + APO and CTL + APO. Serum activity of antioxidant enzymes glutathione peroxidase, superoxide dismutase (SOD), and catalase was lower in DM than CTL; apocynin restored catalase and SOD levels in DM + APO. Myocardial NADPH oxidase activity did not differ between groups.ConclusionApocynin restores serum antioxidant enzyme activity despite unchanged myocardial NADPH oxidase activity in diabetic rats.

Exploring the Mechanism of Skeletal Muscle in a Tacrolimus-Induced Posttransplantation Diabetes Mellitus Model on Gene Expression Profiles

“…Research studies have shown that PTDM increase the risk of cardiovascular events including acute myocardial infarction [25]. DM damages the cardiac contractile and relaxation function and is associated with acute myocardial infarction due to hypertrophied [26,27]. It has been reported that DM induces skeletal muscle atrophy [15][16][17], and our research found that Tac-induced PTDM can induce skeletal muscle atrophy.…”

The effect of folic acid administration on cardiac tissue matrix metalloproteinase activity and hepatorenal biomarkers in diabetic rats

“…), dissolved in physiological saline (0.9 % NaCl, 1 D r a f t ml/kg b.w.). Citrate buffer is used for dissolving STZ more frequently than physiological saline (Gimenes et al 2018;Gimenes et al 2015). In order to avoid the effects of citrate buffer on the tested parameters, we used a physiological saline to dissolve STZ, but because of that we applied a higher dose of STZ.…”

“…In order to avoid the effects of citrate buffer on the tested parameters, we used a physiological saline to dissolve STZ, but because of that we applied a higher dose of STZ. After 72h fasting blood glucose level was measured, and a glucose level higher than 12.2 mmol/l was considered as a positive for DM (Gimenes et al 2018). In order to confirm the development of diabetes another control group (C0, n = 8) that received physiological solution in one dose and the DM group were used.…”

Exercise during transition from compensated left ventricular hypertrophy to heart failure in aortic stenosis rats

“…Cardiac structures and LV function were evaluated by transthoracic echocardiogram and tissue Doppler imaging using a commercially available echocardiograph (General Electric Medical Systems, Vivid S6 model, Tirat Carmel, Israel) equipped with a 5-11.5 MHz multifrequency transducer. [30][31][32][33] The rats were anaesthetized with a mixture of ketamine hydrochloride (50 mg/kg) and xylazine hydrochloride (1 mg/kg) intramuscularly. A two-dimensional parasternal short-axis view of the left ventricle was obtained at the level of the papillary muscles.…”