Free radicals and oxidative stress have been implicated in the etiology of diabetes and its complications. This in vivo study has examined whether subacute administration of pycnogenol, a French pine bark extract containing procyanidins that have strong antioxidant potential, alters biomarkers of oxidative stress in normal and diabetic rats. Diabetes was induced in female Sprague-Dawley rats by a single injection of streptozotocin (90 mg/kg body weight, ip), resulting (after 30 days) in subnormal body weight, increased serum glucose concentrations, and an increase in liver weight, liver/body weight ratios, total and glycated hemoglobin, and serum aspartate aminotransferase activity. Normal and diabetic rats were treated with pycnogenol (10 mg/kg body weight/day, ip) for 14 days. Pycnogenol treatment significantly reduced blood glucose concentrations in diabetic rats. Biochemical markers for oxidative stress were assessed in the liver, kidney, and heart. Elevated hepatic catalase activity in diabetic rats was restored to normal levels after pycnogenol treatment. Additionally, diabetic rats treated with pycnogenol had significantly elevated levels of reduced glutathione and glutathione redox enzyme activities. The results demonstrate that pycnogenol alters intracellular antioxidant defense mechanisms in streptozotocin-induced diabetic rats.

Diabetes mellitus is characterized by hyperglycemia and, in chronic disease, by microvascular pathologies, especially in the kidney, peripheral nerve, and eye. Although hyperglycemia can be controlled with insulin and/or antihyperglycemic medications, diabetic retinopathy continues to be the leading cause of blindness in the United States. Because increased oxidative stress may be a cause of retinopathy, this study examined the hypothesis that administration of exogenous antioxidants can restore a more balanced oxidative condition. Normal and 30-day streptozotocin-induced diabetic Sprague-Dawley rats received daily intraperitoneal doses (10 mg/kg) of beta-carotene, alpha-lipoic, and Pycnogenol individually or in combinations for 14 days, after which retinae were dissected and fractionated for the assay of activities of glutathione reductase, glutathione peroxidase, gamma-glutamyl transferase, and superoxide dismutase. In normal rats, treatment with antioxidant combinations led to a decrease in gamma-glutamyl transferase activity; beta-carotene plus pycnogenol treatment decreased the activity of both glutathione-related enzymes. Decreased retinal gamma-glutamyl transferase activity of diabetic rats was normalized by the administration of pycnogenol alone or in combination with beta-carotene. In diabetic rats, retinal glutathione reductase activity increased after treatment with beta-carotene alone or with pycnogenol. Treatment with pycnogenol and alpha-lipoic acid alone or in combination decreased the activity of glutathione peroxidase, while this activity was increased after treatment with a combination of all antioxidants. Elevated activity of superoxide dismutase in diabetic retina was normalized by treatment with alpha-lipoic acid and with pycnogenol and beta-carotene in combination, but not with all three together. Antioxidants can access the retina and, once there, can alter antioxidant enzyme activities. In both normal and diabetic rats, combinations of antioxidants have different effects on retinal antioxidant enzyme activities than do individual antioxidants.

Increasing interest in the role of oxidative stress and beta-carotene in disease and prevention led us to examine the results of beta-carotene's administration in diabetic rats, a model for high-oxidative stress. In this experiment, amounts of lipid peroxidation, glutathione, and glutathione disulfide, and activity levels of catalase, glutathione peroxidase, glutathione reductase, superoxide dismutase, and gamma-glutamyl transpeptidase were measured in the liver, kidney, and heart of Sprague-Dawley rats with streptozotocin-induced diabetes, and after treatment with 10 mg/kg/day of beta-carotene for 14 days. Beta-carotene treatment resulted in the reversal of the diabetes-induced increase in hepatic and cardiac catalase activity, the decreased levels of glutathione disulfide in the heart, and the increased cardiac and renal levels of lipid peroxidation. Treatment with beta-carotene exacerbated the increased glutathione peroxidase activity in the heart and the decreased catalase activity in the kidneys. In contrast to reduced hepatic glutathione levels in untreated diabetic rats, beta-carotene treatment increased glutathione levels in diabetic rats. Increased hepatic gamma-glutamyl transpeptidase activity in diabetic rats was not reduced by treatment. Thus, beta-carotene therapy for 14 days prevented/reversed some, but not all, diabetes-induced changes in oxidative stress parameters.

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