Antioxidant Status and Biomarkers of Oxidative Stress in Dogs with Diabetes Mellitus
Increasing evidence implicates oxidative damage in the progression and pathologic complications of human diabetics. This study assessed antioxidant status and oxidative stress in dogs with diabetes mellitus (DM). Antioxidant status was measured in diabetic (n=10) and control (n=10) dogs by HPLC of vitamin E isomers, reduced (GSH) and oxidized glutathione (GSSG), and calculation of the GSH:GSSG ratio. Biomarkers of protein, lipid and DNA peroxidation (fructosamine, isoprostanes, and Comet assay, respectively), and neutrophil function were used to evaluate oxidative stress. Correlation between glycemic control and antioxidant status/ oxidative stress was also investigated. A diabetic index was generated using clinical signs, body condition score, insulin dose, fructosamine, fasted blood glucose and urinary glucose and ketones. Diabetic dogs were separated into those with good (n=4) or poor (n=6) control.
Serum fructosamine concentration was significantly higher (DM = 472.9 mmol/l, controls 281.3 mmol/l; p<0.0001), while specific vitamin E isomers, serum GSH (DM = 885.8 ng/ml, controls = 1188.1 ng/ml, p=0.01) and 8-F2α-isoprostanes (DM = 0.31 ng/ml, controls = 3.74 ng/ml; p<0.0001) were significantly lower in diabetic dogs versus controls. Antioxidant status/ oxidative stress was not associated with glycemic control in diabetic dogs.
Despite strong association of DM with oxidative stress in humans, this simple relationship is not found in diabetic dogs. They have both increased and decreased parameters of systemic oxidative stress compared with control dogs. This may be due to higher levels of antioxidants in canine therapeutic diets, the relatively short duration of disease in dogs compared to humans, or other factors.