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It is well known that reperfusion damage of ischemic myocardium may be attributed to alterations in the antioxidant defense system against free radical aggression. In addition, the degree of myocardial damage may depend on the duration and severity of ischemia that precedes reperfusion. We carried out serial ischemic experiments (10, 30, 60 and 120 min) in ex-vivo rat hearts followed by 30 min reperfusion and we assayed the glutathione-dependent enzymatic activities (selenium-dependent glutathione-peroxidase: GSH-Px; selenium-independent glutathione peroxidase: GST-Px; glutathione-transferase: GST and glutathione-reductase: GS-SG-Red), Catalase activity (CAT) and non-proteic thiol compounds (NP-SH) at the end of reperfusion. We found a significant reduction of NP-SH, GSH-Px and CAT in ischemic/reperfused hearts from 30 min on, while GST activity was increased. In addition, we observed the appearance of a selenium-independent glutathione peroxidase activity (GST-Px) belonging to the GST system. In conclusion, we found the longer the duration of ischemia the greater the inbalance between the myocardial antioxidant system especially the GST activation, suggesting in particular for GST-Px, a role in the control of the damage against oxygen toxicity during ischemia/reperfusion.

In 6 normal rabbits, the aortic arch, the descending thoracic and the abdominal aorta were tested for non proteic thiol compounds, selenium-dependent and selenium-independent glutatione peroxidase, glutatione reductase, glutatione transferase and thiobarbituric acid reactive substances. The aortic arch showed the greatest content of non proteic thiol compounds and thiobarbituric acid reactive substances, associated to the highest activities of glutathione-related enzymes. However, not significant differences were detectable between aortic arch and descending thoracic aorta, except for the glutathione transferase activity (0.395 +/- 0.031 vs 0.330 +/- 0.053 U/mg protein, p less than 0.05). Furthermore, both aortic arch and descending thoracic aorta showed significantly higher values of non proteic thiol compounds (46.05 +/- 10.15% and 33 +/- 13.5%, p less than 0.05), selenium-dependent glutathione peroxidase activity (70.35 +/- 26% and 54.3 +/- 9.5%, p less than 0.05), glutathione reductase activity (25.4 +/- 7% and 18.4 +/- 4.5%, p less than 0.05) and thiobarbituric acid reactive substances (65.8 +/- 18% and 47.2 +/- 17%, p less than 0.05) with respect to the abdominal aorta. The selenium-independent glutathione peroxidase activity was not detectable. In conclusion, a biochemical gradient in glutathione-related antioxidant defences and thiobarbituric acid reactive substances proceeding from the proximal to the distal segments seems to exist in the normal rabbit aorta. These results could contribute to explain the non homogeneous distribution of experimental atherosclerosis in the rabbit aorta.

In 24 rabbits fed a hyperlipidic diet (0.5% cholesterol, 5% lard and 5% peanut oil) for 10 (group A1), 30 group B1) and 60 days, (Group C1), compared to 24 control rabbits fed a standard diet for the same periods, antioxidant defence system (total superoxide dismutase, catalase, total thiol compounds selenium-dependent and selenium-independent glutathione peroxidase, glutathione reductase, glutathione transferase) and lipid peroxidation (thiobarbituric acid-reactive substances) in the aortic wall were tested. The percent of intima with grossly apparent atherosclerosis, is assessed by staining with the lipophilic dye Sudan IV, was negligible in group A1, but increased progressively in groups B1 (22.7-6.7%) and C1 (56.8-8.8%). Compared to the controls, a significant rise in superoxide dismutase activity was observed after 30 days of hyperlipidic diet, with a further marked increase at 60 days. Total thiol compounds and selenium-dependent glutathione peroxidase activity rose progressively from 10 to 30 and 60 days in cholesterol-fed rabbits. On the contrary, catalase, glutathione reductase and glutathione transferase activities significantly decreased in all experimental groups. Selenium-independent glutathione peroxidase activity was not detectable. Thiobarbituric acid-reactive substances increased about 3 times in hyperlipidemic rabbits. In conclusion, the changes in aortic antioxidant defence mechanisms and lipid peroxidation precede the massive vascular lipid infiltration in cholesterol-fed rabbits; some antioxidant mechanisms are stressed (superoxide, dismutase, glutathione peroxidase, total thiol compounds), whereas others are depressed (catalase, glutathione reductase, and glutathione transferase), thus potentially reducing or increasing vascular susceptibility to oxidative injury.

The aim of this study was to investigate the clinical efficacy of oral Pycnogenol® (Horphag Research Ltd, United Kingdom) in patients with diabetic microangiopathy. Patients without a history of diabetic ulcerations were treated with Pycnogenol, Patients received oral Pycnogenol (50 mg capsules, 3 times daily for a total of 150 mg daily for 4 weeks). A group of 30 patients was included (severe microangiopathy); 30 comparable patients were observed as controls (no treatment during the observation period). All patients (age, 59 years; range, 55–68 years; male:female = 18:12) included in the treatment group completed the 4-week study. Also, all controls completed the follow-up period. There were no drop-outs. All included subjects had signs and symptoms of diabetic microangiopathy. The duration of diabetes—from the first signs/symptoms-was on average 7.5 years (SD = 3). After 4 weeks, microcirculatory and clinical evaluations showed a progressive decrease in skin flux at rest in the foot (indicating an improvement in the level of microangiopathy), a significant decrease in capillary filtration, and a significant improvement in the venoarteriolar response in all treated subjects. There were no visible effects in controls except a slight reduction in skin flux at rest in the foot. Treatment was well tolerated in both groups. In conclusion, this study confirms the clinical efficacy of Pycnogenol in patients with diabetic microangiopathy. The study indicates the clinical role of Pycnogenol in the management, treatment, and control of this common clinical problem. The treatment may be also useful to prevent diabetic ulcerations by controlling the level of microangiopathy. [ABSTRACT FROM AUTHOR]