Effects of repeated desflurane and sevoflurane anesthesia on enzymatic free radical scavanger system.

BACKGROUND: To investigate the possible effects of repeated sevoflurane and desflurane anesthesia on hepatocellular system by evaluating the free radical metabolism, hepatocellular enzymes and histopatholgical changes in rats. METHODS: Four groups of animals were studied. Sevoflurane 2% (v/v) and desflurane 6% (v/v) in air/O2 were administered to animals in group II (n=9) and III (n=9) respectively. 100% (v/v) O(2) was administered in group IV (n=9). Administration was done for 60 minutes over 3 days. Nine animals were allocated to control group (group I), superoxide dismutase (SOD), catalase (CAT), glutathion peroxidase (GSH-Px), glutathione-s-transferase (GST) and thiobarbituric acid reactive substances (TBARS) were studied. Also electron microscopy was performed. RESULTS: Catalase, SOD, GSH-Px, GST activities and TBARS levels were significantly higher in groups II and III than in group I (p<0.05). All parameters were significantly higher in groups II versus group IV (p<0.05). On the other hand, SOD, GSH-Px and GST activities were significantly elevated in group III than IV, but CAT activity and TBARS levels were not significantly. Catalase, SOD, GSH-Px, GST but not TBARS levels were significantly higher in groups II and III than in group IV (p<0.05). TBARS levels were higher in group III than in group IV, but this elevation was not statistically significant. CAT, SOD and GSH-Px activities were significantly higher in groups II than in group III (p<0.05). CONCLUSION: Although electron microscopy findings were similar for group II and III, we can conclude that sevoflurane might cause more cellular damage than desflurane by causing higher activation of free radical metabolising enzymes.

Oxidative stress and antioxidant status in elderly diabetes mellitus and glucose intolerance patients.

Increased oxidative stress and impaired anti-oxidant defense have been suggested as contributory factors for initiation and progression of complications in diabetes mellitus. Aging itself has been shown to be along with increased oxidative stress and lower anti-oxidant defense. We aimed at investigating oxidative stress and anti-oxidant enzymes in 61 elderly subjects. Fifteen healthy individuals (group 1, mean age 72.2 +/- 5.13), 13 glucose intolerant patients (group 2, mean age 71.7 +/- 4.9), 19 patients with type 2 diabetes mellitus (T2DM) without any complication (group 3, mean age 70.0 +/- 6.0), and 14 patients with T2DM with at least one complication (group 4, mean age 69.8 +/- 4.7) were included in the study. Whilst plasma levels for malondialdehyde (MDAP) and erythrocyte malondialdehyde (MDAE) were measured as markers of oxidative stress, activity of erythrocyte superoxide dismutase (SOD), glutathion peroxidase (GSH-Px), and catalase (CAT) were taken as markers of oxidative defense system. MDAP level was significantly elevated in group 4 (P = 0.001). MDAE was elevated in patients with T2DM, particularly in group 4, however, the difference between the groups was of borderline significance (P = 0.07). Whilst CAT was elevated in groups 3 and 4 compared to control subjects (P = 0.025 and 0.002, respectively), no difference was found for SOD between the groups. GSH-Px activity was found to be increased in groups 2, 3 and 4, it did not reach statistical significance (P = 0.106). There were significant correlations between CAT and MDAE (P < 0.0001, r = 0.056) and MDAP (P = 0.016, r = 0.306). These results suggest that there was an increased oxidative stress in elderly diabetics, however, this is not due to reduced erythrocyte antioxidant defense potential but, rather, increased free radical production possibly due to hyperglycemia.

N-acetylcysteine in intestinal reperfusion injury: an experimental study in rats.

BACKGROUND: The aim of the present study was to investigate the effect of N-acetylcysteine on intestinal reperfusion injury. METHODS: Forty Sprague-Dawley rats were divided into four groups (n = 10): sham, sham + N-acetylcysteine, reperfusion, and reperfusion + N-acetylcysteine. Thirty minutes of ischaemia +/- 30 min of reperfusion was performed under 100 mg/kg N-acetylcysteine or placebo, administered 30 min before the operation in the groups where appropriate. Ileum samples were resected for histopathologic evaluation and tissue malondialdehyde and super oxide dismutase level determination. RESULTS: The mean mucosal injury score and malondialdehyde level of the reperfusion and reperfusion + N-acetylcysteine groups were significantly higher than that of the control and control + N-acetylcysteine group (P < 0.01, P < 0.05, respectively). Mean super oxide dismutase level of the control + N-acetylcysteine group was significantly higher than that of the other groups (P < 0.05). CONCLUSION: N-Acetylcysteine did not prevent intestinal reperfusion injury by means of histopathologic findings and malondialdehyde level.

Pentose phosphate pathway, glutathione-dependent enzymes and antioxidant defense during oxidative stress in diabetic rodent brain and peripheral organs: effects of stobadine and vitamin E.

The aim of the present study was to investigate the effects of treatment with antioxidant stobadine (ST) on the activities of enzymes related with pentose phosphate pathway and glutathione-dependent metabolism and the other markers of oxidative stress in brain and peripheral organs of diabetic rats, and to compare the effects of ST treatment alone with the effects of treatments with another antioxidant vitamin E and ST plus vitamin E. Rats were made diabetic by the injection of streptozotocin (STZ; 55 mg/kg IP), and, 2 days later, some control and diabetic rats were left untreated or treated with ST (24.7 mg/kg/day, orally), vitamin E (400-500 U/kg/day, orally), or both substances together. In the brain, although 6-phosphogluconate dehydrogenase activity (6-PGD) did not change, glucose-6-phosphate dehydrogenase activity (G-6PD) was markedly increased in diabetic rats compared with controls; only combined treatment with ST and vitamin E produced a partial prevention on this alteration. The aorta G-6PD and 6-PGD of diabetic rats were 52% and 36% of control values, respectively. Neither single treatments with each antioxidant nor their combination altered the G-6PD and 6-PGD in aorta of diabetic rats. Glutathione peroxidase (GSHPx) activity was increased by STZ-diabetes in brain, heart, and kidney. In diabetic brain, vitamin E alone or combination with ST kept GSHPx at normal levels. Diabetes-induced stimulation in GSHPx did not decrease in response to the treatment with vitamin E in heart and kidney, but was greatly prevented by ST alone. The activity of glutathione reductase (GR) was decreased in brain and heart of diabetic rats. The treatment with each antioxidant or with a combination of both agents completely prevented this deficiency and resulted in further activation of GR in diabetic tissues. Glutathione S-transferase (GST) activity did not significantly change in diabetic brain and aorta. GST was stimulated by all treatment protocols in the brain of diabetic rats and was depressed in aorta of control rats. Catalase (CAT) was activated in diabetic heart but depressed in diabetic kidney. Diabetes-induced abnormalities in CAT activity did not respond to vitamin E alone in heart, was moderately ameliorated by the treatment with this vitamin in kidney, and was completely prevented by ST alone in both tissues. Superoxide dismutase (SOD) activity of brain and heart was unchanged by the diabetes but inhibited in diabetic kidney after the treatment ST alone or ST plus vitamin E. The lipid peroxidation (MDA) was increased in diabetic brain and heart. ST or vitamin E alone partly prevented diabetes-induced increase in MDA in brain and heart; however, antioxidant combination achieved a completely amelioration in MDA of these tissues of diabetic rats. Kidney MDA levels were similar in control and untreated diabetic animals. ST and vitamin E treatments, when applied separately or together, significantly reduced kidney MDA in both control and diabetic rats; and the combined effect of antioxidants was greater than that of each alone. These results are consistent with the degenerative role of hyperglycemia on cellular reducing equivalent homeostasis and antioxidant defense, and provide further evidence that pharmacological intervention of different antioxidants may have significant implications in the prevention of the prooxidant feature of diabetes and protects redox status of the cells.

Effects of vitamin A and insulin on the antioxidative state of diabetic rat heart: a comparison study with combination treatment.

Because elevated oxidative stress may exacerbate cardiovascular complications of diabetes mellitus, the current study aimed to investigate the effects of treatment with either vitamin A, an antioxidant, or with insulin on lipid peroxidation products and antioxidant enzyme activities of diabetic rat heart. Also to evaluate whether a combination of vitamin A and insulin exerts more beneficial effects than treatment with each agent alone. Rats were made diabetic with a single injection of streptozotocin (STZ, 55 mg kg(-1) i.p.). Two days after STZ-injection, one group of diabetic rats was treated with vitamin A (retinol acetate, 30 mg kg(-1) day(-1) i.o.) for 12 weeks. A second group of diabetic rats was untreated for 6 weeks and then treated for another 6 weeks with insulin (8-10 IU rat(-1) day(-1) s.c.). Both therapies were applied to another group of diabetic rats for assessment of combined therapy with vitamin A plus insulin. Hearts from 12-week untreated diabetic animals showed about a four-fold increase in the level of thiobarbituric acid reactive substances (TBARS), indicative of increased lipid peroxidation. This was accompanied by approximately 100% increase in both catalase and glutathione peroxidase (GSHPx) enzyme activities. Therapy with insulin alone caused a small but significant improvement in plasma TBARS as well as GSHPx activities, but no significant change in plasma catalase in diabetic animals. Diabetes-induced disturbance in TBARS was almost completely prevented by vitamin A therapy. Although, a similar degree of activities for GSHPx was determined in diabetic animals treated with each agent alone, combination therapy was found to be more effective than single therapies in the recovery of GSHPx of diabetic heart. In contrast to insulin single therapy, vitamin A alone significantly prevented an increase in catalase activity of diabetic heart, and a combination of these agents did not supply any further benefit. Superoxide dismutase (SOD) activity was not found significantly different among the experimental groups. STZ-diabetes also resulted in less plasma retinol and retinol-binding protein (RBP), which was significantly improved by insulin single therapy while vitamin A used alone, failed to increase plasma retinol and RBP levels of diabetic animals. Our findings suggest that single therapy with insulin is unable to preclude oxidative reactions in diabetic heart to the same extent as obtained by vitamin A therapy alone, in spite of allowing recovery of normal growth rate and improved vitamin A metabolism in diabetic rats. A combination of insulin with vitamin A may provide more benefits than use of either agent alone in the treatment of general characteristics of diabetes and the maintenance of antioxidant defence of diabetic heart and thus in the reduction of peroxidative stress-induced cardiac injury.