<p>Lycopene Improves the Metformin Effects on Glycemic Control and Decreases Biomarkers of Glycoxidative Stress in Diabetic Rats</p>

Abstract

Introduction Oxidative stress and exacerbated generation of advanced glycation end products (AGEs) participate in the onset of diabetic complications. Lycopene is a potent antioxidant; evidence accounts for its ability to mitigate diabetic disturbances, including the deleterious events of advanced glycation. Therefore, this carotenoid has emerged as a candidate to be used in combination with antidiabetic drugs, such as metformin, attempting to counteract the glycoxidative stress. This study investigated the effects of the treatments with lycopene or metformin, alone or in combination, on glycoxidative stress biomarkers and antioxidant defenses in diabetic rats. Methods Streptozotocin-induced diabetic rats were treated for 35 days with lycopene (45 mg/kg) or metformin (250 mg/kg), alone or as mixtures in yoghurt. Plasma levels of glucose, triglycerides, cholesterol, thiobarbituric acid reactive substances and protein carbonyl groups (biomarkers of oxidative damage), fluorescent AGEs (biomarkers of advanced glycation), and paraoxonase 1 activity (antioxidant enzyme) were assessed. Changes in the hepatic and renal levels of glycoxidative damage biomarkers and the activities of antioxidant enzymes were investigated. Results The combination of lycopene with metformin maintained the beneficial effects of the isolated treatments, improving the glucose tolerance and lipid profile, lessening biomarkers of oxidative damage, and increasing the paraoxonase 1 activity. Besides, the combined therapy caused further decreases in postprandial glycemia, plasma levels of cholesterol and AGEs, avoided lipid peroxidation (plasma, kidney), and increased antioxidant defenses, mainly the activity of superoxide dismutase (liver, kidney), indicating the maintenance of the lycopene effects. Conclusion Lycopene combined with metformin may act synergistically in the control of postprandial glycemia, dyslipidemia and glycoxidative stress, as well as increased antioxidant defenses, arising as a promising therapeutic strategy to mitigate diabetic complications.

Lycopene Improves Bone Quality and Regulates AGE/RAGE/NF-кB Signaling Pathway in High-Fat Diet-Induced Obese Mice

“…We demonstrated that lycopene treatment decreases the expressions of AGEs and RAGE as well as inhibits NF-кBp65 activation in the femurs and tibias of obese mice. These results were in line with the findings that lycopene is able to decrease the levels of plasma AGEs and renal RAGE [ 52 ] and suppress NF-кB activation in hyperglycemia rats and HK-2 cells [ 49 , 52 , 53 ]. In addition, lycopene was reported to inhibit ROS-induced NF-кB activation in pancreatic cancer cells [ 54 ].…”

“…The sustained high levels of ROS may be associated with heightened AGE expressions upon hyperglycemia stimulation [ 49 ], which further induces NF-кB activation and subsequent bone resorption [ 50 , 51 ]. We demonstrated that lycopene treatment decreases the expressions of AGEs and RAGE as well as inhibits NF-кBp65 activation in the femurs and tibias of obese mice.…”

Tomatoes: An Extensive Review of the Associated Health Impacts of Tomatoes and Factors That Can Affect Their Cultivation

“…Figueriredo et al [ 275 ] reported that a combination of lycopene with metformin had an additive effect on improvements in postprandial blood glucose levels, dyslipidaemia, and antioxidant status. The investigation was performed in rats, and STZ-induced diabetic rats were treated with lycopene (45 mg/kg) and metformin (250 mg/kg) alone and in combination for 35 days.…”

Beneficial Effect of Lycopene on Diabetes Mellitus and its Possible Mechanism: A Review

“…Although insulin and anti-diabetic drugs are usually effective, most therapies fail to control long-term hyperglycemia. 6 This can actually be overcome by increasing the dose of the drug, but the risk of side effects will also increase, especially in patients with impaired kidney function, it may cause problems. [6][7][8] In addition, it can also be treated with combination therapy, either with conventional anti-diabetic drugs from different groups or with natural bioactive compounds.…”

“…6 This can actually be overcome by increasing the dose of the drug, but the risk of side effects will also increase, especially in patients with impaired kidney function, it may cause problems. [6][7][8] In addition, it can also be treated with combination therapy, either with conventional anti-diabetic drugs from different groups or with natural bioactive compounds. [9][10][11] One of the natural bioactive compounds that has received much attention because it has great potential in the treatment and prevention of chronic diseases is lycopene.…”