Abstract

Combination therapy using natural antioxidants to manage diabetes mellitus and its complications is an emerging trend. The aim of this study was to investigate the changes promoted by treatment of streptozotocin (STZ)-diabetic rats with yoghurt enriched with the bioactives curcumin, lycopene, or bixin (the latter two being carotenoids). Antioxidants were administered individually, or as mixtures, and biomarkers of metabolic and oxidative disturbances, particularly those associated with cardiovascular risk, were assessed. Treatment of STZ-diabetic rats with natural products individually decreased glycemia, triacylglycerol, total-cholesterol, oxidative stress biomarkers, including oxidized low-density lipoprotein (ox-LDL), and increased the activities of antioxidant enzymes. Individual carotenoids increased both high-density lipoprotein (HDL) and paraoxonase levels, whereas curcumin increased only paraoxonase. Treatments with mixtures of curcumin and lycopene or bixin had combined effects, decreasing biomarkers of carbohydrate and lipid disturbances (curcumin effect), increasing the HDL levels (carotenoids effects) and mitigating oxidative stress (curcumin and carotenoids effects). The combined effects also led to prevention of the LDL oxidation, thereby mitigating the cardiovascular risk in diabetes. These findings provide evidence for the beneficial effect of curcumin and carotenoid mixtures as a supplementation having antioxidant and antiatherogenic potentials, thus appearing as an interesting strategy to be studied as a complementary therapy for diabetic complications.

Highlights

  • Diabetes mellitus (DM) is a chronic endocrine syndrome resulting from a deficiency in pancreatic insulin production and/or insulin resistance in target tissues, leading to various abnormalities in carbohydrate, lipid, and protein metabolism [1]

  • Normal or diabetic rats treated with yoghurt were considered the control groups related to the absence (NYOG) or the presence (DYOG) of metabolic disturbances arising due to insulin deficiency

  • Diabetic rats were sorted into seven groups (10 rats/group) as follows: diabetic rats treated with yoghurt (DYOG); 90 mg/kg curcumin in yoghurt (DC); 5.5 mg/kg bixin in yoghurt (DB); 90 mg/kg curcumin + 5.5 mg/kg bixin (DCB) in yoghurt; 45 mg/kg lycopene in yoghurt (DL); 90 mg/kg curcumin + 45 mg/kg lycopene (DCL) in yoghurt; 4U insulin (DINS)

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Summary

Introduction

Diabetes mellitus (DM) is a chronic endocrine syndrome resulting from a deficiency in pancreatic insulin production and/or insulin resistance in target tissues, leading to various abnormalities in carbohydrate, lipid, and protein metabolism [1]. DM can lead to a variety of microvascular (diabetic nephropathy, retinopathy, and neuropathy) and macrovascular (atherosclerosis, coronary artery diseases, and stroke) complications; these are the major causes of morbidity and mortality in diabetes [2]. Individuals with DM have many of the risk factors associated with cardiovascular disease (CVD) [6]. CVD is the leading cause (approximately 70%) of death in people with DM [7]. A combination of various factors, including oxidative stress, endothelial dysfunction, and low-grade inflammation, accounts for the increased risk of CVD in people with diabetes [8]. Oxidative stress in DM originates from the increased production of reactive oxygen species (ROS) mostly arising from increased mitochondrial electron transport chain activity [9] caused by hyperglycemia. Oxidative stress in DM is widely accepted to be an important component in the production of oxidized LDL (ox-LDL) [10]

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