A Classic Citrus Monoterpene Revisited: Protective Effects of D-Limonene on Hepatic and Aortic Vascular Dysfunctions in Type 1 Diabetic Rats

Background: Diabetes mellitus is a metabolic disturbance characterized by chronic hyperglycemia, which stems from defective secretion and/or action of insulin. D-Limonene has been studied for the confirmation of its antidiabetic and antioxidant effects. This paper aims to investigate the antidiabetic and antioxidants effects of D-Limonene in an experimental model of DM1. Methods: Female Wistar rats (180–250g) received streptozotocin (STZ, 45 mg/kg) intraperitoneally. Animals with capillary glycemia ≥ 250 mg/dL were considered diabetic. D-Limonene at oral doses of 12.5 mg/kg, 25 mg/kg and 50 mg/kg was administered during 28-day treatment. Water and food intake, weight gain and capillary glycemia were evaluated. At the end of the treatment, the following biochemical parameters were assessed: serum glucose, HbA1c, urea, creatinine, AST, ALT, GGT, ALP and albumin. The oxidative stress markers were determined in plasma, erythrocytes, and aortic homogenates: malondialdehyde, nitrite, myeloperoxidase, superoxide dismutase and catalase. Results: D-Limonene (25 and 50 mg/kg) significantly reduced serum glucose, HbA1c, AST, ALT, GGT and ALP when compared to DC, as well as plasma MDA and nitrite concentrations. Interestingly, D-Limonene (25 and 50 mg/kg) decreased both plasma and aortic myeloperoxidase activities, as well as increased both erythrocytic and aortic catalase activities. Conclusions: These findings, besides a marked D-Limonene-induced hypoglycemic effect, pave the way for further studies comprising a multi-target treatment by providing benefits on hepatic and vascular complications related to the diabetic condition.