Abstract
Prediabetes is an intermediate hyperglycaemic state which has been associated with cardiovascular dysfunction. However, cardiovascular dysfunction is not only caused by intermediate hyperglycaemia but also endothelial dysfunction, inflammation, and oxidative stress associated with prediabetes. Bredemolic acid (BA), an isomer of maslinic acid, has been reported to ameliorate the intermediate hyperglycaemia found in prediabetes; however, the effects of this triterpene on cardiovascular function have not yet been determined. Therefore, this study investigated the effects of BA on cardiovascular function in diet-induced prediabetic rats. Thirty-six male rats that weighed 150–180 g were divided into two groups, the non-prediabetic (n = 6) and the prediabetic groups (n = 30), which were fed normal diet (ND) and HFHC diet, respectively. The prediabetic rats were further subdivided into five groups (n = 6) and treated with either BA (80 mg/kg) or metformin (MET, 500 mg/kg) every third day for 12 weeks. After 12 weeks, blood samples and the heart were collected for biochemical analysis. The untreated prediabetic rats showed a significant increase in body mass index (BMI), waist circumference (WC), blood pressure, heart rate, lipid profile, lipid peroxidation, and inflammatory markers with significant decrease in endothelial function and antioxidant biomarkers by comparison with the non-prediabetic animals. The administration of BA significantly improved cardiovascular functions such as blood pressure, heart rate, and endothelial function. There was also a significant decrease in BMI, WC, lipid profile, lipid peroxidation, and inflammation with a concomitant increase in antioxidant capacity. BA administration improved cardiovascular function by attenuation of oxidative stress, inflammatory, and endothelial dysfunction markers.
Highlights
Type 2 diabetes mellitus (T2DM) is a heterogeneous metabolic disorder which is associated with cardiovascular diseases (CVDs), that is often preceded by the onset of prediabetes [1]
Insulin resistance is associated with decreased nitric oxide (NO) production due to inhibition of endothelial nitric oxide synthase via impaired phosphatidylinositol 3 kinase (PI3K)–AKT pathway [9]. e decreased NO production causes an imbalance in the vascular endothelial tone which triggers vasoconstriction followed by increased heart rate and high blood pressure [9, 10]
Thirty-six male Sprague Dawley rats with body weight 150–180 g were used. e rats were obtained and bred at the Biomedical Research Unit (BRU), University of KwaZulu-Natal (UKZN). e animals were kept and maintained in standard experimental conditions at room temperature (22 ± 2°C), humidity (55 ± 5%), and 12 h day :12 h night cycle. e animals consumed standard rat chow (Meadow Feeds, South Africa) and water ad libitum for 2 weeks to acclimatize before being exposed to the experimental diet. e high fat high carbohydrate (HFHC) diet was composed of carbohydrates (55% kcal/g), fats (30% kcal/g), and proteins (15% kcal/g)
Summary
Type 2 diabetes mellitus (T2DM) is a heterogeneous metabolic disorder which is associated with cardiovascular diseases (CVDs), that is often preceded by the onset of prediabetes [1]. One of the identified causes of this disorder is chronic consumption of high caloric diets which are rich in carbohydrates as well as saturated and polyunsaturated fats coupled with sedentary lifestyles [2, 3]. This leads to inefficient metabolism of carbohydrates and fats resulting in accumulation of intracellular and extracellular glucose and lipids known as glucolipotoxicity [4]. Previous studies have shown that intermediate hyperglycaemia below the level used to define diabetes mellitus is a risk factor for CVD development [13, 14]
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