Combined Effects of Curcumin and Lycopene or Bixin in Yoghurt on Inhibition of LDL Oxidation and Increases in HDL and Paraoxonase Levels in Streptozotocin-Diabetic Rats

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.

Curcumin improves the effect of a reduced insulin dose on glycemic control and oxidative stress in streptozotocin‐diabetic rats

“…The overproduction of ROS and the decreased levels of antioxidant defenses contribute to the establishment of oxidative stress in DM (Maritim, Sanders, & Watkins, ). In agreement with this, DYOG rats had high levels of oxidative damage biomarkers, including plasma TBARS (Figure a) and hepatic PCO (Figure b) and low activity of antioxidant enzymes (Figure ), corroborating the results from previous studies (Arcaro et al, ; Assis et al, ). Structural modifications due to oxidative or glycative stress may explain the low activity of antioxidant enzymes in diabetes (Pigeolet et al, ; Yan & Harding, ).…”

“…The antidiabetic activity of curcumin has been well documented in both type 1 (Gutierres et al, ) and type 2 (Shao et al, ) DM models, improving not only the levels of glycemia but also those of dyslipidemia and tissue damage markers. Previous studies carried out by groups from our laboratory (Arcaro et al, ; Assis et al, ) and by others (Ghosh, Bhattacharyya, Rashid, & Sil, ) have found that the treatment of diabetic rats with curcumin is able to reduce in vivo oxidative stress. These findings identify curcumin as a promising adjunct to insulin therapy for diabetes.…”

“…The treatment of STZ‐diabetic rats with 4‐U/day insulin is often used as an effective intervention for the control of glycemia levels and to normalize diabetic disturbances. This dose of insulin has been administered to diabetic rats as a positive control in previous studies by our laboratory (Arcaro et al, ; Assis et al, ; Gutierres et al, ) and also in studies by other groups using the experimental model of type 1 DM (Palma et al, ; Slaughter et al, ). In fact, STZ‐diabetic rats with initial glycemia values of approximately 470 mg/dl, when treated with 4‐U/day insulin, they had a biomarker profile practically identical to that of normal rats.…”

“…A wide range of protective effects against the metabolic disturbances associated with DM have been attributed to curcumin (Gutierres et al, ; Kunnumakkara et al, ; Mantzorou, Pavlidou, Vasios, Tsagalioti, & Giaginis, ; Pagano, Romano, Izzo, & Borrelli, ; Zhang, Fu, Gao, & Liu, ). Studies on the combination of curcumin with oral antidiabetic drugs or other natural antioxidants have obtained promising results of additive or combined beneficial effects on the biomarkers altered in diabetes (Assis et al, ; Attia et al, ). Interestingly, Palma et al () found that when diabetic rats were treated for 30 days with a combination of insulin (4 U/day) and curcumin (60 mg/kg), no additive effects were found on glycemia reduction nor in biomarkers related to hepatic and renal damage, lipid peroxidation (LPO), or superoxide dismutase (SOD) activity, in relation to the treatment with insulin alone (4 U/day).…”

Lycopene Ameliorated Oxidative Stress and Inflammation in Type 2 Diabetic Rats

“…The hypothesis is that lycopene could protect the biomolecules, such as lipids, proteins, and DNA, against being oxidized via blocking the damage from ROS (Rao, Ray, & Rao, ). In different disease models, lycopene has been reported possessing capacities in ameliorating oxidative stress by reducing malondialdehyde (MDA), TNF‐α, and oxidized low‐density lipoprotein (ox‐LDL) (Assis et al., ; Murillo, DiMarco, & Fernandez, ; Pierine et al., ; Yin et al., ). Besides its antioxidant properties, lycopene was also reported to possess biological activities, such as facilitating gap junction communication, stimulating the immune system, modulating endocrine‐mediated pathways, and regulating cell cycle (Rao et al., ).…”