Supplementation with alpha-tocopherol or a combination of alpha-tocopherol and ascorbic acid protects the gastrointestinal tract of iron-deficient rats against iron-induced oxidative damage during iron repletion

Recently we have shown the susceptibility of Fe-deficient rat intestine to oxidative damage during Fe repletion. The role of dietary antioxidants like ascorbic acid, alpha-tocopherol and a combination of both in counteracting the oxidative stress was tested in this study. Five groups of thirteen weanling WKY female rats were fed with an Fe-deficient diet for a period of 5 weeks. Another set of thirteen rats received an Fe-sufficient diet and served as the control group (Con). Oral administration of either vehicle (D), 8 mg Fe alone (D+) or in the presence of 24 mg ascorbic acid (D+ + C), 40 mg alpha-tocopherol (D+ + E) or a combination of both (D+ + C + E) per d for 15 d was carried out in Fe-depleted rats. The impact of this treatment protocol on Fe status, oxidative stress and antioxidant status at the site of Fe absorption was assessed. It was observed that though the indicators of Fe status were normalised on Fe supplementation, the oxidative stress as reflected by the levels of both thiobarbituric-acid reactive substances (TBARS) and protein carbonyls were significantly greater in D+ and D+ + C compared to D+ + E, D+ + C + E and Con groups. The mucosal cell DNA damage was seen in D+, D+ + C and D+ + E groups on electrophoresis. Functional integrity as assessed by the activities of alkaline phosphatase and lys-ala-dipeptidyl aminopeptidase were normalized in all the groups treated with the antioxidant(s). There were significant positive alterations in some of the endogenous antiperoxidative systems and in serum caeruloplasmin activity in D+ + E and D+ + C + E groups. Paradoxically, serum ascorbate levels were significantly lower in D+ + C than in D+ + E and D+ + C + E groups. This could be due to the protection offered by alpha-tocopherol in the presence of Fe. It is concluded that supplementation of alpha-tocopherol alone or in combination with ascorbic acid protects the gastrointestinal tract of Fe-deficient rats against Fe-mediated oxidative damage during Fe repletion. However, ascorbic acid alone does not protect the gastrointestinal tract against Fe-induced oxidative stress.     

Lutein interacts with ascorbic acid more frequently than with alpha-tocopherol to alter biomarkers of oxidative stress in female zucker obese rats

The influence of dietary lutein, with and without moderate amounts of vitamin C (VC) or vitamin E (VE), on biomarkers of oxidative stress was examined in rats. Nine groups of immature Zucker obese (fa/fa) and lean female rats (8/group) consumed ad libitum for 8 wk the AIN-93G diet (Control) to which was added either dl-alpha-tocopherol acetate (VE) at 0.60 mg/kg or ascorbic acid (VC) at 0.75 mg/kg diet. Each of these diets contained lutein oil (FloraGlo) at 0.5 (Lut0.5) or 1.0 (Lut1.0) mg/kg diet. Weight gain, food efficiency and relative liver weight were higher in obese than in lean rats. Although liver malondialdehyde (MDA) concentrations were significantly higher in obese than in lean rats, levels were significantly lower in obese rats fed VE, VE-Lut and VC-Lut0.5 compared with other obese groups. The accumulation of alpha-tocopherol in liver was 6- and 3-times greater in the VE and VE-Lut1.0 groups, respectively, compared with the obese and lean control groups. Lutein reduced the activity of superoxide dismutase (SOD) in obese rats, independent of VC or VE, and raised the activity of glutathione peroxidase to higher levels in lean rats when combined with VC. Plasma insulin levels were dramatically higher in obese compared with lean rats, but significantly lower in obese rats fed VC-Lut0.5, VE-Lut1.0 and Lut1.0 compared with the Control group. These results suggest that lutein independently reduces the activity of SOD and alters more biomarkers of oxidative stress when combined with vitamin C than with vitamin E, and that vitamin E reduces liver lipid peroxidation in obese rats when the accumulation of liver alpha-tocopherol is very high.     

Effect of astaxanthin in combination with alpha-tocopherol or ascorbic acid against oxidative damage in diabetic ODS rats

The present study was performed to investigate the effect of astaxanthin in combination with other antioxidants against oxidative damage in streptozotocin (STZ)-induced diabetic Osteogenic Disorder Shionogi (ODS) rats. Diabetic-ODS rats were divided into five groups: control, astaxanthin, ascorbic acid, alpha-tocopherol, and tocotrienol. Each of the four experimental groups was administered a diet containing astaxanthin (0.1 g/kg), in combination with ascorbic acid (3.0 g/kg), alpha-tocopherol (0.1 g/kg), or tocotrienol (0.1 g/kg) for 20 wk. The effects of astaxanthin with other antioxidants on lipid peroxidation, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) excretion, serum creatinine (Cr) level, creatinine clearance (Ccr), and urinary protein content were assessed. The serum lipid peroxide levels and chemiluminescent (CL) intensity in the liver of the alpha-tocopherol and tocotrienol groups were significantly reduced in comparison to that of the control group. In the alpha-tocopherol group, urinary 8-OHdG excretion, serum Cr level, Ccr, urinary albumin excretion, and urinary protein concentration were significantly decreased as compared with those in the control group. Additionally, the CL intensity in the kidney of the alpha-tocopherol group was significantly lower, but that of the ascorbic acid group was significantly higher than that in the control group. These results indicate that dietary astaxanthin in combination with alpha-tocopherol has an inhibitory effect on oxidative stress. On the other hand, our study suggests that excessive ascorbic acid intake increases lipid peroxidation in diabetic rats.     

The levels of lycopene, alpha-tocopherol and a marker of oxidative stress in healthy northeast Thai elderly

An imbalance between oxidative stress and antioxidant capacity has been proposed to play an important role in the development and progression of chronic diseases in the elderly. The present study was carried out to investigate correlation between the serum antioxidants (lycopene and alpha-tocopherol) and malondialdehyde (MDA), a marker of oxidative stress in the healthy Thai elderly. The 207 healthy subjects aged 60-91 years old (72 males and 135 females) in Khon Kaen province, Thailand were enrolled in this study. They were interviewed by questionnaires about smoking habit. Serum lycopene and alpha-tocopherol levels were determined by high performance liquid chromatography (HPLC). MDA was measured by thiobarbituric assay. Serum lycopene and alpha-tocopherol levels in the elderly were 0.27 micromol/L (95% CI = 0.23-0.31) and 22.10 micromol/L (95% CI = 20.99-23.22), respectively. Males had significant lower serum lycopene and alpha-tocopherol levels than females (p<0.001). Of 72 males, 31.94% are current smokers whereas 1.4% of 135 females are current smokers. Current smokers had significantly lower serum lycopene (0.17 +/- 0.11 micromol/L) than current non-smokers (0.28 +/- 0.27 micromol/L) (p=0.0439) but level of alpha-tocopherol had non significance (p=0.210). Moreover, the current smokers had higher MDA malondialdehyde level (1.55 +/- 0.10 micromol/L) than the current non-smokers (1.35 +/- 0.04 micromol/L) (p=0.094). Thus, dietary antioxidant supplementation from local fruits and vegetables may have a beneficial role in the prevention of chronic diseases at high-risk oxidative stress such as smoking in these elderly.     

Prolonged marginal ascorbic acid deficiency induces oxidative stress in retina of guinea pigs

We examined whether prolonged marginal ascorbic acid deficiency induces oxidative stress in the retina of guinea pigs. Male guinea pigs aged four weeks were given a scorbutic diet (20 g/animal per day) with either marginally deficient ascorbic acid (0.5 mg/animal per day) or adequate ascorbic acid (1 g/animal per day) in drinking water for three and six months. The retinal contents of the reduced form of ascorbic acid in the deficient group at three and six months were 68.1 and 43.5%, respectively, of that in the corresponding adequate group. The retinal contents of the oxidized form of ascorbic acid in the deficient group at three and six months were 1.9- and 2.7-fold, respectively, higher than that in the corresponding adequate group. The content of retinal thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, in the deficient group was 2.5-fold higher than that in the adequate group at six months. The retinal contents of reduced glutathione (GSH) in the deficient group at three and six months were 84.8 and 66.7%, respectively, of that in the corresponding adequate group. The deficient group had 37.5% of retinal vitamin E content of the adequate group at six months. The deficient group had higher serum vitamin E concentration than the adequate group in both experimental periods. There were no differences in serum TBARS and GSH concentrations between the groups at both periods. These results indicate that prolonged marginal ascorbic acid deficiency induces oxidative stress in the retina of guinea pigs without systemic oxidative stress.     

Relative activity of alpha-tocopherol and gamma-tocopherol in preventing oxidative red cell hemolysis.

The purpose of this study was to compare the antioxidant activities of alpha-tocopherol and gamma-tocopherol in protecting the red cell membrane against lipid peroxidation. Tocopherols were incorporated into the red cell membrane by incubating cells with solutions of the tocopherols in bovine albumin. The cells were then washed and subjected to the dialuric acid hemolysis test. Analysis of variance of the response curves revealed that gamma-tocopherol had 38% of the activity of alpha-tocopherol. No evidence was found for an interaction between the two tocopherols when present in the red cell membranes simultaneously.     

Daidzein is more efficient than genistein in preventing ovariectomy-induced bone loss in rats

We investigated the ability of genistein and daidzein, two soybean isoflavones, compared with that of 17 alpha-ethinylestradiol, to prevent bone loss in ovariectomized rats, a model for postmenopausal osteoporosis. Female Wistar rats (n = 65; 12 mo old) were either sham-operated (SH; n = 13) or ovariectomized (OVX; n = 52). On d 0, OVX rats were randomly assigned to groups as follows: 13 received genistein [G; 10 mcg/(g body weight. d)], 13 were treated with daidzein [D; 10 mcg/(g body weight. d)], 13 received 17 alpha-ethinylestradiol [E(2); 30 mcg/kg body weight. d)] and 13 were untreated (OVX). Compounds were mixed with a soy protein-free powdered semipurified diet and given orally for 3 mo. On d 90, the bone mineral density (BMD) in lumbar vertebrae, femur and its metaphyseal and diaphyseal zones (rich in cancellous and cortical bone, respectively) was lower in OVX than in SH (P < 0.01). In D or E(2), the four BMD were not different from SH, whereas in G, only the diaphyseal BMD was not different from SH. Image analysis performed in the distal femur metaphysis revealed that the cancellous bone area was lower in OVX than in SH (P < 0.01). Only the area in D was not different from that in SH. Finally, the bone turnover, which was higher in OVX than in SH (P < 0.005 and P < 0.05 for plasma osteocalcin concentration and urinary deoxypyridinoline excretion, respectively), was not different in G, D or E(2) compared with SH. Therefore, consumption of 17 alpha-ethinylestradiol or daidzein was more efficient than genistein in preventing ovariectomy-induced bone loss in rats.     

Effect of ascorbic acid-rich diet on in vivo-induced oxidative stress

Using hyperbaric oxygen (HBO) therapy as an in vivo oxidation model, we investigated the effect of a diet enriched in ascorbic acid (AA) on HBO-induced oxidative stress. Volunteers (n 46) were allocated to the AA-rich diet group or the control group. Blood samples were collected at the basal time, after the 1-week diet before and immediately after the HBO treatment, and 1 week after the HBO treatment. AA level, total antioxidant status (TAS), hydroperoxides (HP), lymphocyte DNA oxidation and DNA repair capacity were assessed. The expression of genes involved in oxidative stress was evaluated in lymphocytes and the protein activity of the modulated genes was determined in the plasma. The AA level and the antioxidant status of plasma were increased by AA-rich food consumption. HBO exposure did not affect the AA levels or TAS, but induced HP formation in the control group. The lymphocytes isolated from dietary-supplemented subjects were resistant to ex vivo DNA oxidation, showing an increased DNA repair capacity compared with controls. A difference in gene expression pattern was observed between the groups. AA-rich foods provide dual protection against oxidative stress, enhancing plasma antioxidant levels and stimulating genes involved in cell detoxification.     

Relations of serum ascorbic acid and alpha-tocopherol to diabetic retinopathy in the Third National Health and Nutrition Examination Survey

The protective relation of ascorbic acid and alpha-tocopherol to the development of diabetic retinopathy has not been thoroughly evaluated in epidemiologic studies. The association of prevalent diabetic retinopathy with serum ascorbic acid and alpha-tocopherol was studied among participants with type 2 diabetes (>or=40 years) (n = 998) in the Third National Health and Nutrition Examination Survey (1988-1994); 20% of the sample (n = 199) had prevalent retinopathy. The overall odds ratio for retinopathy among participants in quartile 4 compared with quartile 1 for serum ascorbic acid was 1.3 (95% confidence interval: 0.8, 2.3), with a p for trend = 0.60 after adjustment for the confounders of smoking, race, waist/hip ratio, hypertension, and duration of diabetes. The overall odds ratio for retinopathy among participants in quartile 4 compared with quartile 1 for serum alpha-tocopherol was 2.7 (95% confidence interval: 1.6, 4.6), with a p for trend = 0.14 after adjustment for confounders. After removal of supplement users of vitamin C (n = 307) or vitamin E (n = 298), the odds ratio changed direction or was attenuated: adjusted odds ratios for retinopathy among participants in quartile 4 compared with quartile 1 for serum ascorbic acid and alpha-tocopherol = 0.7 (95% confidence interval: 0.3, 1.4) and 1.6 (95% confidence interval: 0.9, 2.9), respectively. In summary, no significant associations were observed between serum levels of major dietary antioxidants and retinopathy. Recent use of supplements for treatment of complications of diabetes may explain the direct associations.     

Supplementation of fenugreek leaves reduces oxidative stress in streptozotocin-induced diabetic rats

Trigonella foenum-graecum, commonly known as fenugreek, is a traditional medicinal plant of the Leguminoseae family in India. The antioxidant effect of fenugreek leaves was evaluated in the streptozotocin-induced diabetic rat model. The antioxidant effect was evaluated by estimating thiobarbituric acid-reactive substances and reduced glutathione and measuring the activities of catalase and superoxide dismutase in liver, heart, and kidney in diabetic rats. Fenugreek leaf powder supplementation significantly lowered lipid peroxidation and significantly increased the antioxidant system in diabetic rats. The effect at a dose of 1 g/kg of body weight of fenugreek leaf powder was similar to that of glibenclamide. Insulin restores all the parameters to near normal values. Thus, fenugreek leaf powder reduces oxidative stress in experimental diabetes.     

Effect of nickel exposure on peripheral tissues: role of oxidative stress in toxicity and possible protection by ascorbic acid

The vast industrial use of nickel has led to environmental pollution by the metal and its by-products during production, recycling, and disposal. Nickel is a known hematotoxic, immunotoxic, hepatotoxic, pulmotoxic, and nephrotoxic agent. Allergic skin reactions are common in individuals who are sensitive to nickel. This article presents a selective review on nickel and its effect on certain metabolically active peripheral tissues of human and animals. The subtopics include nickel sources and uses, exposure pathways, transport, excretion, general health effects, and specific acute and chronic nickel toxicities in peripheral tissues like liver, lungs, and kidneys. The review particularly addresses the nickel-induced generation of reactive oxygen species and increased lipid peroxidation in various metabolically active tissues in humans and animals, and the possible role of vitamin c as a protective antioxidant.     

Role of flavonoids on oxidative stress and mineral contents in the retinoic acid-induced bone loss model of rat

Purpose

Reactive oxygen species play a role in a number of degenerative conditions including osteoporosis. Flavonoids as phyto-oestrogens exert physiological effects against oxidative stress diseases. We developed a retinoic acid-induced bone loss model of rats to assess whether flavonoids and alendronate as positive control have role against oxidative stress and mineral contents in osteoporosis in vivo.

Methods

Three-month-old female rats of the Y59 strain were given quercetin, chrysin, naringenin (100 mg kg^?1) or alendronate (40 mg kg^?1, a positive control) immediately before retinoic acid treatment (80 mg kg^?1) once daily for 14 days by a single intragastric (i.g.) application. In the second part of the study, we assessed the effect of those flavonoids on the skeletal system of healthy rats using single i.g. application on the respective flavonoids during 14 days. Twenty-four hours after the treatment, we analysed bone mineral density and the total content of bone calcium and phosphorus in the femur, the geometric and physical characteristics of thigh bones and lipid peroxidation and glutathione levels of liver and kidney cells.

Results

All flavonoids improved the decrease in bone weight coefficient, the length and the diameter of the bone, the content of bone ash and calcium and phosphorus content induced by retinoic acid. Chrysin and quercetin showed promise as preventive agents. Flavonoids were superior to alendronate according to some criteria.

Conclusions

These results suggest that the dietary flavonoids could reduce retinoic acid-induced oxidative stress and bone loss and that flavonoids may be useful therapeutics for prevention of skeletal diseases.     

Fe2+ and ascorbic acid induced oxidation of cholesterol in phosphatidylcholine liposomes and its inhibition by alpha-tocopherol

Fe2+ and L-ascorbic acid induced oxidation of cholesterol was investigated in liposomes of egg yolk phosphatidylcholine (PC). Cholesterol 5,6-epoxide, 7-hydroxycholesterol, 7-oxocholesterol, and cholestane-3,5,6-triol were detected as the oxidation products by gas chromatography, indicating that epoxidation and hydroperoxidation took place independently in cholesterol. Oxidation of cholesterol was accompanied with oxidative loss of unsaturated fatty acid moiety of PC. When egg yolk PC was replaced by dimyristoyl-PC, little oxidation was observed in the cholesterol fraction. These results indicate that cholesterol oxidation depends on peroxidation of polyunsaturated fatty acids in liposomal phospholipids. alpha-Tocopherol incorporated into liposomes at a level of 1.0 mol% to egg yolk completely suppressed not only the loss of unsaturated fatty acid moiety, but also oxidation of cholesterol. alpha-Tocopherol may inhibit cholesterol oxidation by suppressing phospholipid peroxidation. tert-Butyl hydroxytoluene, a synthetic antioxidant, was less effective against the oxidation of both PC and cholesterol.     

Nutritional status and oxidative stress in an elderly Sardinian population

Weight loss and overweight/obesity-frequent consequences of malnutrition-may impair functional status and worsen concomitant morbidities in the elderly, often through changes in oxidative balance. In order to verify the relationships between these factors, a group of elderly people living on the island of Sardinia (Italy) underwent health and nutritional status assessment and oxidative balance evaluation. The elderly subjects had significantly higher d-ROMs test and body mass index (BMI) values than controls (d-ROMs 325.4 ± 66.3 vs. 295.4 vs 58-9 CARR U, p = 0.006; BMI 28.0 ± 4.6 vs. 21.7 ± 1.4 kg/m², p < 0.0001). The risk of malnutrition in the elderly subjects was evaluated with the Mini Nutritional Assessment (MNA), which showed that 32 of the 111 elderly subjects (28.8%) were at risk of malnutrition, of whom 11 (34%) were overweight and 10 (31-2%) obese. Oxidative stress was negatively and significantly correlated with nutritional status. Oxidative stress may precede malnutrition, even in the absence of weight loss. Routine evaluation of nutritional status and oxidative balance in the elderly may help identify an early risk of malnutrition so that treatment can be personalized.     

Relation of ascorbic acid to bone mineral density and self-reported fractures among US adults

Ascorbic acid is an essential nutrient involved in collagen formation, and its deficiency is associated with abnormal bone development. To examine the relation of ascorbic acid to bone mineral density and the prevalence of self-reported fractures, the authors analyzed data collected from 13,080 adults enrolled in the Third National Health and Nutrition Examination Survey (NHANES III) during 1988-1994. Because they identified three-way interactions among smoking, history of estrogen use, and dietary and serum ascorbic acid in postmenopausal women, they analyzed these relations stratified by smoking and estrogen use. Dietary ascorbic acid intake was independently associated with bone mineral density among premenopausal women (p = 0.002). Among men, serum ascorbic acid was associated in a nonlinear fashion with bone mineral density (p < 0.05), and dietary ascorbic acid intake was associated in a nonlinear fashion with self-reported fracture (p = 0.05). Among postmenopausal women without a history of smoking or estrogen use, serum ascorbic acid was unexpectedly associated with lower bone mineral density (p = 0.01). However, among postmenopausal women with a history of smoking and estrogen use, a standard deviation increase in serum ascorbic acid was associated with a 49% decrease in fracture prevalence (p = 0.001). Dietary and serum ascorbic acid measures were associated inconsistently with bone mineral density and self-reported fracture among adult participants in NHANES III.     

Serum ascorbic acid and HDL cholesterol in a healthy elderly Japanese population

The relationships between HDL cholesterol and serum ascorbic acid were examined in 79 male and 96 female healthy elderly Japanese, aged 60 and over. A significant positive correlation between serum HDL cholesterol and ascorbic acid was observed both in males (r = .243, p less than 0.05) and in females (r = .376, p less than 0.01). The results of multiple regression analyses indicated that serum ascorbic acid is a predictor of serum HDL cholesterol accounting for about 5% and 11% of its total variation in male and female subjects, respectively. The effect of age, BMI, status of physical activity, alcohol ingestion and cigarettes consumption, serum triglycerides and total cholesterol were taken into account as potentially confounding variables.