Combined Effects of Lycopene and Metformin on Decreasing Oxidative Stress by Triggering Endogenous Antioxidant Defenses in Diet-Induced Obese Mice.

Since lycopene has antioxidant activity, its combination with metformin may be useful to contrast diabetic complications related to oxidative stress. This study aimed to investigate the effects of metformin combined with lycopene on high-fat diet (HFD)-induced obese mice. Seventy-two C57BL-6J mice were divided into six groups: C (control diet-fed mice), H (HFD-fed mice for 17 weeks), H-V (HFD-fed mice treated with vehicle), H-M (HFD-fed mice treated with 50 mg/kg metformin), H-L (HFD-fed mice treated with 45 mg/kg lycopene), and H-ML (HFD-fed mice treated with 50 mg/kg metformin + 45 mg/kg lycopene). Treatments were administered for 8 weeks. Glucose tolerance, insulin sensitivity, fluorescent AGEs (advanced glycation end products), TBARS (thiobarbituric acid-reactive substances), and activities of antioxidant enzymes paraoxonase-1 (PON-1; plasma), superoxide dismutase, catalase and glutathione peroxidase (liver and kidneys) were determined. Metformin plus lycopene reduced body weight; improved insulin sensitivity and glucose tolerance; and decreased AGEs and TBARS in plasma, liver and kidneys. Combined therapy significantly increased the activities of antioxidant enzymes, mainly PON-1. Lycopene combined with metformin improved insulin resistance and glucose tolerance, and caused further increases in endogenous antioxidant defenses, arising as a promising therapeutic strategy for combating diabetic complications resulting from glycoxidative stress.