The effect of lipoic acid on antioxidant status and lipid peroxidation in rats exposed to chronic restraint stress.

This study was designed to investigate effect of alpha-lipoic acid (LA) on lipid peroxidation, nitric oxide production and antioxidant systems in rats exposed to chronic restraint stress. Twenty four male Wistar rats, aged three months, were divided into four groups: control (C), the group treated with LA (L), the group exposed to restraint stress (S) and the group exposed to stress and treated with LA (LS). Restraint stress was applied for 21 days (1 h/day) and LA (100 mg/kg/day) was injected intraperitonally to the L and LS groups for the same period. Restraint stress significantly decreased brain copper/zinc superoxide dismutase (Cu,Zn-SOD) and brain and retina glutathione peroxidase (GSH-Px) and catalase (CAT) activities compared with the control group. Thiobarbituric acid reactive substances (TBARS), nitrite and nitrate levels were significantly increased in the tissues of the S group compared with the C group. LA produced a significant decrease in brain and retina TBARS, nitrite and nitrate levels of the L and LS groups compared to their corresponding control groups. LA increased all enzyme activities in the tissues of the LS group compared to the S group. Our study indicated that LA is an ideal antioxidant candidate for the prevention of stress-induced lipid peroxidation.

Retinoic acid isomers protect hippocampal neurons from amyloid-beta induced neurodegeneration.

Attenuating amyloid-beta mediated neurodegeneration is of major therapeutic consideration in the potential treatment of Alzheimer disease. Previously, we found that a high dietary consumption of retinoic acid was associated with a reduced incidence of Alzheimer disease. Therefore, in this study, we investigated whether amyloid-beta mediated cell death in primary hippocampal neurons could be prevented by retinoic acid isomers. Our results suggest that retinoic acid isomers, including all-trans retinoic acid, 9-cis retinoic acid, and 13-cis retinoic acid, may play an important role in protecting neurons from amyloid-beta -induced cell death. Retinoic acid may therefore afford a novel therapeutic mechanism for the treatment and prevention of Alzheimer disease.

N-acetyl cysteine, L-cysteine, and beta-mercaptoethanol augment selenium-glutathione peroxidase activity in glucose-6-phosphate dehydrogenase-deficient human erythrocytes.

In glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes, failure to maintain normal levels of reduced glutathione (GSH) due to decreased NADPH regeneration in the hexose monophosphate pathway results in acute hemolytic anemia following exposure to oxidative insults, such as ingestion of Vicia fava beans or use of certain drugs. GSH is a source of protection against oxidative attack, used by the selenium-dependent glutathione peroxidase (Se-GSH-Px)/reductase (GR) system to detoxify hydrogen peroxide and organic peroxides, provided that sufficient GSH is made available. In this study, Se-GSH-Px activity was analyzed in G6PD-deficient patients in the presence of reducing agents such as N-Acetyl cysteine, L-cysteine, and beta-mercaptoethanol. Se-GSH-Px activity was decreased in G6PD-deficient red blood cells (RBCs). N-Acetyl cysteine, L-cysteine, and beta-mercaptoethanol increased Se-GSH-Px activity in G6PD-deficient human erythrocytes, indicating that other reducing agents can be utilized to complement Se-GSH-Px activity in G6PD deficiency. Based on the increased susceptibility of G6PD-deficient patients to oxidative stress, the reported increase in Se-GSH-Px activity can facilitate the detoxification of reactive oxygen species.

L-carnitine protects gastric mucosa by decreasing ischemia-reperfusion induced lipid peroxidation.

Studies have shown that reactive oxygen metabolites and lipid peroxidation play important roles in ischemia-reperfusion injury in many organs such as heart, brain and stomach. The aim of this study is to evaluate the antioxidant effect of L-carnitine on gastric mucosal barrier, lipid peroxidation and the activities of antioxidant enzymes in rat gastric mucosa subjected to ischemia-reperfusion injury. Rats were subjected to 30 min of ischemia followed by 60 min of reperfusion. L-carnitine (100 mg/kg), was given to rats intravenously five minutes before the ischemia. In our experiment, lesion index, thiobarbituric acid reactive substances, prostaglandin E2 and mucus content in gastric tissue were measured. The results indicated that the lesion index and the formation of thiobarbituric acid reactive substances increased significantly with the ischemia-reperfusion injury in the gastric mucosa. L-carnitine treatment reduced these parameters to the values of sham operated rats. The tissue catalase and superoxide dismutase activities and prostaglandin E2 production decreased significantly in the gastric mucosa of rats exposed to ischemia-reperfusion. L-carnitine pretreatment increased the tissue catalase activity and prostaglandin E2 to the levels of sham-operated rats but did not change superoxide dismutase activity. There were no significant difference in glutathione peroxidase activity and mucus content between the groups in the gastric mucosa. In summary, L-carnitine pretreatment protected gastric mucosa from ischemia-reperfusion injury by its decreasing effect on lipid peroxidation and by preventing the decrease in prostaglandin E2 content of gastric mucosa.

The effect of exercise on brain antioxidant status of diabetic rats.

BACKGROUND: To investigate the effect of exercise on brain antioxidant status of diabetic rats. METHODS: Wistar rats were divided into four groups: Control (C), exercise (CE), diabetic (D), and diabetic+exercise (DE). Diabetes was induced by single administration of streptozotocin (60 mg/kg). We used an aerobic exercise program for 8 weeks of CE and DE rats. After the end of the experimental period, Cu, Zn-superoxide dismutase (Cu, Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), xanthine dehydrogenase (XDH) and xanthine oxidase (XO) activities and thiobarbituric acid reactive substances (TBARS) levels of brain were measured. RESULTS: Diabetes caused significant reduction of brain Cu, Zn-SOD and GSH-Px activities in the D and DE groups. CAT activity was decreased only in the D group. Exercise did not alter CAT activity of brain, whereas markedly increased Cu, Zn-SOD activity in the DE group. In contrast to diabetes-related decrease in the activity of Cu, Zn-SOD, increase in the XO and GSH-Px activities were observed in the DE group compared with the D group. XDH activity was significantly reduced in two exercise groups according to the control rats, but the decrease was not accompanied with the activity of XO elevation in all groups. Increase in the XO activity and decrease in the XDH activity in the DE rats have revealed that diabetes and exercise have potentially effect in free radical production. On the other hand, TBARS levels were found to be elevated in all diabetic animals. CONCLUSIONS: Our results show that aerobic exercise did not affect lipid peroxidation of brain, but in diabetic condition improved antioxidant defence.

Effect of the herbicide 4-CPA on human erythrocyte antioxidant enzymes in vitro.

To investigate the possible role of oxygen free radicals and oxidant stress in the toxic effects of phenoxyherbicides, we studied the in vitro effect of 4-chlorophenoxyacetic acid (4-CPA) on various human erythrocyte antioxidant enzymes, namely glucose-6-phosphate dehydrogenase, catalase, selenium-dependent glutathione peroxidase, glutathione reductase and Cu/Zn-superoxide dismutase. 4-CPA added in a dose of 1 ppm to human erythrocytes for 1 h caused a significant reduction in glucose-6-phosphate dehydrogenase (P <0.001) and catalase (P <0.001) activities, but did not significantly affect the activities of other enzymes. Such selective inactivation of specific erythrocyte antioxidant enzymes may play a role in the toxic effects of phenoxyherbicides.

Erythrocyte, plasma, and serum antioxidant activities in untreated toxic multinodular goiter patients.

Erythrocyte, plasma, and serum antioxidant activities were studied in patients with newly diagnosed and untreated toxic multinodular hyperthyroid goiter and compared to healthy control subjects. Erythrocyte antioxidant enzyme activities, glutathione, malondialdehyde, and ceruloplasmin levels were significantly increased, whereas serum vitamin E, plasma vitamin C, and selenium levels were decreased in hyperthyroid patients compared to control subjects. The findings show that untreated toxic multinodular goiter causes profound alterations in components of the antioxidant system in erythrocytes indicative of increased oxidative stress. Taken together, these data suggest that hyperthyroid patients may benefit from dietary supplements of antioxidants.

Effects of propylthiouracil treatment on antioxidant activities in blood of toxic multinodular goiter patients.

Erythrocyte, serum and plasma antioxidant activities and the effects of propylthiouracil (PTU) treatment on these activities were studied in patients with toxic multinodular goiter. The activities of the erythrocyte antioxidant enzymes (glucose-6-phosphate dehydrogenase, catalase, Cu/Zn-superoxide dismutase, selenium (Se)-dependent glutathione peroxidase and glutathione reductase) and the levels of erythrocyte Se, serum ceruloplasmin and plasma malondialdehyde were significantly higher while serum vitamin E, plasma vitamin C and plasma Se were lower in hyperthyroid patients. PTU treatment, not for 1 but for 3 months caused a partial reversal of antioxidant activities to euthyroid levels. It is suggested that alterations in blood antioxidant activities following PTU treatment might be due to the antioxidant and/or antithyroid effect of this drug.

Effects of sulfur dioxide inhalation on antioxidant enzyme activities in rat erythrocytes.

Swiss-Albino male rats were exposed to sulfur dioxide (SO2) (10 ppm) one hour daily for 60 days and the effect on the erythrocyte antioxidant enzyme activities was studied. Erythrocyte glucose-6-phosphate dehydrogenase (G-6-PD), superoxide dismutase (Cu,Zn-SOD), glutathione peroxidase (GSH-Px), catalase (CAT), glutathione-S-transferase (GST) activities and thiobarbituric acid reactive substances (TBARS) of 30 rats (14 controls and 16 sulfur dioxide groups) were measured. There were no significant differences in the catalase and G-6-PD activities of SO2 group as compared with controls. GSH-Px and GST activities in SO2 group were significantly higher than those in the control group. But, there was a significant decrease in the SOD activity. The rate of TBARS formation was enhanced significantly in erythrocytes of the SO2 group relative to the control group. These results reveal that SO2 inhalation enhanced lipid peroxidation in the erythrocyte and influence the antioxidant enzymes of erythrocyte.

Effect of cadmium on antioxidant status in alloxane-induced diabetic rats.

Fifty-two healthy Swiss Male Albino rats aged two mo were used in this study. They were divided into four groups: control (C), diabetic (D), cadmium (Cd), and diabetic + Cd (D + Cd) groups. Diabetic condition was induced in D and D + Cd groups by administration of alloxane (5 mg/100 g). After this treatment, Cd and D + Cd groups were injected with CdCl2 i.p. (2 mg/kg/wk). At the end of the 2-mo experimental period, thiobarbituric acid reactive substances (TBARS), plasma and erythrocyte selenium (Se), plasma ceruloplasmin (Cp), and vitamin E (vit E) were determined in four groups of rats. The erythrocyte Se was lower in the experimental groups than in the controls. Plasma Se was significantly decreased in the D and D + Cd groups compared with the control group. Plasma Cp was unaltered. Plasma vit E was significantly decreased in Cd group in comparison with the C, D, and D+Cd groups.

Increased resistance to oxidative stress in normal and glucose-6-phosphate dehydrogenase-deficient hemolysates in the presence of enzyme substrates.

Erythrocytes and hemolysates from 10 normal and 10 glucose-6-phosphate dehydrogenase-deficient individuals were incubated with cumene hydroperoxide, and free radical-induced lipid peroxidation was monitored by chemiluminescence. Chemiluminescence intensities in erythrocytes of normal and deficient subjects were similar in the presence or absence of glucose-6-phosphate dehydrogenase substrates. Hemolysates of normal and deficient subjects also showed similar chemiluminescence in the absence of substrates. However, with the addition of substrates to the incubation medium, deficient hemolysates reached maximum chemiluminescence intensity within a shorter period, and maximum values were higher than in normal hemolysates. We believe this offers a new means of detection of glucose-6-phosphate dehydrogenase-deficient patients.

Erythrocyte selenium-glutathione peroxidase activity is lower in patients with coronary atherosclerosis.

To obtain further insight into the role of erythrocyte antioxidant systems in the development of atherosclerosis, intraerythrocyte enzyme activities and selenium levels in erythrocytes were determined in 37 patients with angiographically proved coronary artery stenosis and 15 subjects with normal coronary angiograms as controls. In a preliminary study, the enzymatic activities of glucose-6-phosphate dehydrogenase (G6PD), glutathione reductase (GR) and selenium-dependent glutathione peroxidase (Se-GPx) were measured in both venous and arterial blood samples obtained from patients before angiography. The data of the preliminary study, which showed that only the Se-GPx decreased in the patients, led us to concentrate on the Se-GPx and Se levels to determine the changes in these variables. Our results showed that there was a decrease in both the activity of Se-GPx and Se levels in erythrocytes parallel to the increase in the severity of coronary artery disease. It was concluded that these parameters might be used as determinants in the assessment of the severity of the disease.

Continuous monitoring of hydroperoxide-induced peroxidation in human erythrocytes by low-level chemiluminescence.

We studied the effect of cumene hydroperoxide, t-butyl hydroperoxide, and hydrogen peroxide on intact healthy human erythrocytes (15 g hemoglobin/dl) using chemiluminescence to monitor peroxidation. We measured the chemiluminescence spectrum, the process of hemolysis, the pH shift, and absorbance spectrum during the incubation with chemicals producing oxidative stress. Maximum chemiluminescence was reached with cumene hydroperoxide at about 50 min, but with t-butyl hydroperoxide at 100 min. The effect of organic hydroperoxide was concentration dependent, whereas the effect of hydrogen peroxide was independent of concentration. Peroxides induced hemolysis after 30 min. The pH shift to alkaline was observed in the first 20-min period. Incubation with organic hydroperoxides induced a decrease in absorption at 580, 545, and 345 nm. Hydrogen peroxide induced a decrease in the same period of time but this returned to the normal range by 120 min. There was no change in absorption at 420 nm with any of the peroxidative agents. Our results suggest that low-level chemiluminescence is a useful model for studying hydroperoxide-induced peroxidation in human erythrocytes.

Erythrocyte glucose-6-phosphate dehydrogenase (1.1.1.49) deficiency in Antalya province, Turkey: an epidemiologic and biochemical study.

Glucose-6-phosphate dehydrogenase (1.1.1.49) activity was assessed in 1986-1988 in blood samples from 1,521 individuals from 375 families living an Antalya city and adjacent villages by Beutler's fluorescence spot test. The families were randomly selected by the State Statistical Institute. Complete deficiency occurred in 7.4% of males and 1.8% of females. Mean enzyme activity was 6.77 +/- 1.07 IU/g Hb in normals and ranged between 0 and 0.48 IU/g Hb in those considered deficient. Kinetic measurements made with partially purified enzyme showed that GdB+ and GdB- variants were present in normal and in deficient subjects, respectively.