Interaction of vitamin E and exercise training on oxidative stress and antioxidant enzyme activities in rat skeletal muscles

It has been shown that free radicals are increased during intensive exercise. We hypothesized that vitamin E (vit E) deficiency, which will increase oxidative stress, would augment the training-induced adaptation of antioxidant enzymes. This study investigated the interaction effect of vit E and exercise training on oxidative stress markers and activities of antioxidant enzymes in red quadriceps and white gastrocnemius of rats in a 2x2 design. Thirty-two male rats were divided into trained vit E-adequate, trained vit E-deficient, untrained vit E-adequate, and untrained vit E-deficient groups. The two trained groups swam 6 h/day, 6 days/week for 8 weeks. The two vit E-deficient groups consumed vit E-free diet for 8 weeks. Vitamin E-training interaction effect was significant on thiobarbituric acid reactive substances (TBARSs), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in both muscles. The trained vit E-deficient group showed the highest TBARS and GPX activity and the lowest SOD activity in both muscles. A significant vit E effect on glutathione reductase and catalase was present in both muscles. Glutathione reductase and catalase activities were significantly lower in the two vit E-adequate groups combined than in the two vit E-deficient groups combined in both muscles. This study shows that vit E status and exercise training have interactive effect on oxidative stress and GPX and SOD activities in rat skeletal muscles. Vitamin E deprivation augmented the exercise-induced elevation in GPX activity while inhibiting exercise-induced SOD activity, possibly through elevated oxidative stress.     

Biochemical effects of pretreatment with vitamins E and C in rats submitted to intrastriatal hypoxanthine administration

We previously demonstrated that intrastriatal injection of hypoxanthine, the major metabolite accumulating in Lesch-Nyhan disease, inhibited Na+,K+-ATPase activity and induced oxidative stress in rat striatum. In the present study, we evaluated the action of vitamins E and C on the biochemical alteration induced by hypoxanthine administration on Na+,K+-ATPase, TBARS, TRAP, as well as on superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GPx) activities in striatum of adult rats. Animals received pretreatment with vitamins E and C or saline during 7 days. Twelve hours after the last injection of vitamins or saline, animals were divided into two groups: (1) vehicle-injected group and (2) hypoxanthine-injected group. For all parameters investigated in this research, animals were sacrificed 30 min after drug infusion. Results showed that pretreatment with vitamins E and C prevented hypoxanthine-mediated effects on Na+,K+-ATPase, TBARS and antioxidant enzymes (SOD, CAT and GPx) activities; however the reduction on TRAP was not prevented by these vitamins. Although extrapolation of findings from animal experiments to humans is difficult, it is conceivable that these vitamins might serve as an adjuvant therapy in order to avoid progression of striatal damage in patients affected by Lesch-Nyhan disease.     

The effects of isosorbide dinitrate on methemoglobin reductase enzyme activity and antioxidant states

Isosorbide dinitrate (ISDN) has been used in the treatment of ischaemic cardiovascular diseases for many years. ISDN is the most popular nitric oxide donor and causes methemoglobinemia as an important side-effect. The purpose of this study was to examine antioxidant states and methemoglobin reductase activity after giving ISDN and ISDN plus vitamin E. Rats were divided into three groups according to the treatment: control group, ISDN group and ISDN plus vit. E group. We measured reduced glutathione in blood (GSH), plasma malondialdehyde (MDA), erythrocyte superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and NADH-dependent methemoglobin reductase activities. In the ISDN group, plasma MDA levels were significantly high compared to the control and ISDN + vit. E groups (p < 0.001). In the ISDN and ISDN + vit. E groups, blood GSH levels were higher than those of the control group (p < 0.05). Changes of SOD and GPx activities were not significant. In the ISDN and ISDN + vit. E groups the erythrocyte catalase and NADH-dependent methemoglobin reductase activities were significantly higher than that in the control group (p < 0.001). We conclude that oxidant drugs such as ISDN need to be carefully used because of lipid peroxidation and methemoglobinemia. These findings support the notion that vitamine E protects tissues against oxidative stress.     

Impact of green tea on oxidative stress induced by ammonium metavanadate exposure in male rats

Transitional metals, as vanadium, are known to exert noxious effects by generating oxidative stress. Addition of antioxidants in the diet could decrease the cytotoxic effect related to the oxidative stress. The present study, carried out in Wistar rats, is a contribution to the evaluation of protective effects of green tea Camellia sinensis, which is known to be rich in antioxidant compounds (polyphenols...). Rats were divided into four groups: (C) was control, (V) was given ammonium metavanadate (AMV), (TH) was given herbal tea as drink (66 g/l) and TH + V was given tea and metavanadate. Group (TH) was given herbal tea one month before vanadium treatment. Metavanadate was daily i.p. injected (5 mg NH4VO3/kg body weight) for 10 days. (C) and (TH) groups received i.p. injections of 0.9% NaCl during the same period. Changes in lipid peroxidation levels (TBARS) in kidney, liver and testes, serum concentrations of vitamins E and A and superoxidismutase (SOD) and catalase (CAT) activities in blood cells were determined. One month pre-treatment with green tea, followed by 10 days of treatment (TH) did not change TBARS in liver and testes as compared to controls, but induced a clear decrease of TBARS in kidneys. Intraperitoneal administration of AMV to rats (V) induced a time-dependant increase of TBARS in kidney, liver and testes that was lowered in rats (V + TH) drinking tea. Vitamin E concentrations were found to be drastically decreased from day 1 to 10 in rats (V). Vitamin A concentration was decreased at day 10 only. Drinking tea lowered AMV inhibitory effects in rats (V + TH), and conversely an increase of vitamins A and E concentrations were found at day 10. SOD and catalase activities were found increased in the blood cells from day 1 to day 5 and conversely decreased at day 10. In contrast, associated to green tea, AMV did not affect SOD and catalase activities compared to controls.     

Protecting antioxidative effects of vitamins E and C in experimental physical stress

Like every redox-active compound vitamin E may exert pro-oxidative and antioxidative effects depending on the reaction partners present. In this work we evaluated the intensity of oxidative stress produced by a physical exercise through swimming as well as of protecting action of antioxidant vitamins E and C. Antioxidant systems include antioxidant enzymes: superoxide-dismutase (SOD), catalase (CAT), glutathion peroxidase (GSH-Px), as well as of components with an antioxidant action of the reduced glutathion type (GSH) and vitamins E and C. We determine the activities of these enzymes in the erythrocytes and heart homogenate. Our results points out a protective effect against oxidative stress produced by swimming in animals treated with vitamins E and C, which are expressed through the diminution of the malondialdehyde (MDA) quantity both in erythrocytes and in the heart, and through the conservation of GSH content in both products. CAT and GSH-Px activities decrease while that of SOD increases on both tissues, but with different intensities in accordance with the variation of protection degree performed by the vitamin couple on these tissues. The obtained data underline the necessity of intensifying the means of endogenous antiradical defence with exogenous antioxidant vitamins C and E. This study highlights the need of a proper vitamin supplement in organism under stress.     

Beneficial effect of succinic acid monoethyl ester on erythrocyte membrane bound enzymes and antioxidant status in streptozotocin-nicotinamide induced type 2 diabetes

Succinic acid monoethyl ester (EMS) was recently proposed as an insulinotropic agent for the treatment of non-insulin dependent diabetes mellitus. In the present study the effect of EMS and metformin on erythrocyte membrane bound enzymes and antioxidants activity in plasma and erythrocytes of streptozotocin-nicotinamide induced type 2 diabeteic model was investigated. Succinic acid monoethyl ester was administered intraperitonially for 30 days to control and diabetic rats. The effect of EMS on glucose, insulin, hemoglobin, glycosylated hemoglobin, TBARS, hydroperoxide, superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (Gpx), glutathione-S-transferase (GST), vitamins C and E, reduced glutathione (GSH) and membrane bound enzymes were studied. The effect of EMS was compared with metformin, a reference drug. The levels of glucose, glycosylated hemoglobin, TBARS, hyderoperoxide, and vitamin E were increased significantly whereas the level of insulin and hemoglobin, as well as antioxidants (SOD, CAT, Gpx, GST, vitamin C and GSH) membrane bound total ATPase, Na(+)/K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase were decreased significantly in streptozotocin-nicotinamide diabetic rats. Administration of EMS to diabetic rats showed a decrease in the levels of glucose, glycosylated hemoglobin, lipid peroxidation markers and vitamin E. In addition the levels of insulin, hemoglobin, enzymic antioxidants, vitamin C, and GSH and the activities of membrane bound enzymes also were increased in EMS and metformin treated diabetic rats. The present study indicates that the EMS possesses a significant beneficial effect on erythrocyte membrane bound enzymes and antioxidants defense system in addition to its antidiabetic effect.     

Effect of vitamin E and selenium on antioxidant enzymes in brain,kidney and liver of cigarette smoke-exposed mice

The present study was conducted to evaluate the protective effects of vitamin E and selenium (Se) application on alteration of antioxidant enzyme activities against cigarette smoking induced oxidative damage in brains, kidneys and liver of mice. Male mice (balb/c) were exposed to cigarette smoke and treated with Se and/or vitamin E. Glutathione transferase (GST), glutathione peroxidase (GPX), glutathione reductase (GRX), superoxide dismutase (SOD) and catalase (CAT) enzyme activities in mice brain, kidney and liver were measured spectrophotometrically. GST, GPX, GRX, SOD and CAT enzyme activities in the brains of smoke-exposed mice were found lower than the enzymes activities of control mice and Se-and vitamin E-treated mice at the end of the three and five months. Opposite to brain, enzyme activities in kidneys and livers of smoke-exposed mice were found higher than the enzymes activities of control mice and Se-and vitamin E-treated mice at the end of the three and five months. Activities of GST, GPX, GRX SOD and CAT in the livers, kidneys and brains of smoke-exposed mice were found statistically different (p < 0.01) compared to control mice and Se-and vitamin E-treated mice. Combined application of vitamin E and Se had an additive protective effect against changing enzymes activities in smoke-exposed mice livers, kidneys and brains at the end of the both application periods. These results suggest that cigarette smoke exposure enhances the oxidative stress, thereby disturbing the tissue antioxidant defense system and combined application of vitamin E and Se protects the brain, kidney and liver from oxidative damage through their antioxidant potential.     

Vitamins C and E improve rat embryonic antioxidant defense mechanism in diabetic culture medium.

BACKGROUND: Diabetes teratogenicity seems to be related to embryonic oxidative stress and the extent of the embryonic damage can apparently be reduced by antioxidants. We have studied the mechanism by which antioxidants, such as vitamins C and E, reduce diabetes-induced embryonic damage. We therefore compared the antioxidant capacity of 10.5-day-old rat embryos and their yolk sacs cultured for 28h in diabetic culture medium with or without vitamins C and E. METHODS: The embryos were cultured in 90% rat serum to which 2mg/ml glucose, 2mg/ml beta hydroxy butyrate (BHOB) and 10 microg/ml of acetoacetate were added. Rat embryos were also cultured in a diabetic medium with 25 microg/ml of vitamin E and 50 microg/ml of vitamin C. Control embryos were cultured in normal rat serum with or without vitamins C and E. RESULTS: Decreased activity of Cu/Zn superoxide dismutase (SOD) and of catalase (CAT) in the "diabetic" embryos and their yolk sacs, and reduced concentrations of low molecular weight antioxidant (LMWA) were found. Under these conditions we also found a decrease in vitamin C and vitamin E concentrations in the embryos, as measured by HPLC. In situ hybridization for SOD mRNA showed a marked reduction of SOD mRNA in the brain, spinal cord, heart and liver of embryos cultured in diabetic medium in comparison to controls. Following the addition of vitamins C and E to the diabetic culture medium, SOD and CAT activity, the concentrations of LMWA, the levels of vitamin C and E and the expression of SOD mRNA in the embryos and yolk sacs returned to normal. CONCLUSIONS: Diabetic metabolic factors seem to have a direct effect on embryonic SOD gene and perhaps genes of other antioxidant enzymes, reducing embryonic endogenous antioxidant defense mechanism. This in turn may cause a depletion of the LMWA, such as vitamins C and E. The addition of these vitamins normalizes the embryonic antioxidant defense mechanism, reducing the damage caused by the diabetic environment.     

Activity of Cassia auriculata leaf extract in rats with alcoholic liver injury

This study was undertaken to investigate the effect of Cassia auriculata leaf extract on tissue lipid peroxidation and antioxidant status in experimental hepatotoxicity. Administering ethanol to rats for 60 days resulted in significantly elevated levels of serum total bilirubin, aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) as compared with those of the experimental control rats. Significantly elevated levels of tissue thiobarbituric acid reactive substances (TBARS), hydroperoxides and lowered activities of superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) were also observed on alcohol treatment as compared with those of experimental control rats. Concentration of serum non-enzymic antioxidants such as vitamin E and vitamin C were also significantly lowered on alcohol supplementation. Treatment with Cassia auriculata leaf extract at a dose of 250 mg kg(-1) body weight and 500 mg kg(-1) body weight to rats administered alcohol, lowered the levels of TBARS and hydroperoxides and elevated the activities of SOD and CAT and the levels of reduced GSH in the liver, brain, kidney and intestine significantly compared to unsupplemented alcohol treated rats. Cassia auriculata leaf extract treatment restored the serum vitamin E, and vitamin C levels also to near those of the experimental control animals. Our data indicate that supplementation with Cassia auriculata leaf extract can offer protection against free radical mediated oxidative stress in experimental hepatotoxicity. In addition, histopathological studies of the liver and brain confirmed the beneficial role of Cassia auriculata leaf extract.     

Systemic oxidative stress in children and teenagers with Down syndrome

Aims

The aim of this study was to evaluate the antioxidant status and oxidative stress biomarkers in the blood of children and teenagers with Down syndrome.

Main methods

The analysis of enzymatic antioxidant defenses, such as the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione transferase (GST), non-enzymatic antioxidants, such as levels of reduced glutathione (GSH), uric acid (UA) and vitamin E, as well as oxidative damage indicators, such as protein carbonyls (PC) levels and lipoperoxidation (TBARS), of DS individuals (n = 20) compared to healthy controls (n = 18). Except the vitamin E was measured by HPLC, all other markers were measured spectrophotometrically.

Key Findings

Antioxidant enzymes analysis showed significant increases in the SOD (47.2%), CAT (24.7%) and GR (49.6%) activities in DS subjects. No significant difference in GPx activity was detected while GST activity (61.2%) was decreased, and both responses may be consequence of the depletion of GSH (24.9%) levels. There were no significant differences in TBARS levels, while PC levels showed decreased (31.7%) levels compared to healthy controls, which may be related to the increase (16.1%) found in serum UA. Levels of vitamin E showed no significant differences between DS individuals compared to controls.

Significance

The results revealed a systemic pro-oxidant status in DS individuals, evidenced by the increased activity of some important antioxidant enzymes, together with decreased GSH levels in whole blood and elevated UA levels in plasma, probably as an antioxidant compensation related to the redox imbalance in DS individuals.     

Oxidative stress in erythrocytes: a study on the effect of antioxidant mixtures during intermittent exposures to high altitude

The aim of our study was to compare and assess the effectiveness of antioxidant mixtures on the erythrocytes (RBC) of adult male albino rats (Wister) subjected to simulated intermittent high altitudes—5,100 m (AL₁) and 6,700 m (AL₂)—to induce oxidative stress (OS). To achieve our objective, we pre-supplemented four sets of animals with different antioxidant mixtures [vitamin E (vit.E; 50 IU/kg BW), vitamin C (vit.C; 400 mg/kg) and l-carnitine (400 mg/kg)] in different combinations [M1 (vit.E+vit.C), M2 (vit.C+carnitine), M3 (vit.E+carnitine) and M4 (vit.C+vit.E+carnitine)] for 30 days prior to as well during exposure to intermittent hypobaric hypoxia (IHH). Membrane instability, in terms of osmotic fragility and hemolysis, decreased in RBCs of supplemented animals. There was a significant increase in the activity of glutathione peroxidase in the RBCs of supplemented animals. We confirmed OS imposed by IHH with assays relating to lipid [thiobarbituric acid reactive substances (TBARS) and lipofuscin (LF)] and protein (carbonyl, PrC) oxidation, and found a positive correlation between PrC and hemolysis, with a decrease in both upon supplementation with M3 and M4 mixtures. Fluorescence microscopic observation showed a maximum decrease in the LF content in rats administered M4 and M1 compared to those on M2 and M3 mixtures at both altitudes. We suggest that multiple antioxidant fortifications are effective in overcoming increased OS experienced by RBCs at high altitudes.     

The effects of diazinon on lipid peroxidation and antioxidant enzymes in rat heart and ameliorating role of vitamin E and vitamin C

Diazinon is one of the most widely used organophosphate insecticides (OPIs) in agriculture and public health programs. Reactive oxygen species (ROS) caused by OPIs may be involved in the toxicity of various pesticides. The aim of this study was to investigate how diazinon affects lipid peroxidation (LPO) and the antioxidant defense system in vivo and the possible ameliorating role of vitamins E and C. For this purpose, experiments were done to study the effects of DI on LPO and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in adult rat heart. Experimental groups were: (1) control group, (2) diazinon treated (DI) group, (3) DI+vitamins E and C-treated (DI+Vit) group. The levels of malondialdehyde (MDA) and the activities of SOD and CAT increased significantly in the DI group compared with the control group. The activity of SOD and the levels of MDA decreased significantly in the DI+Vit group compared with the DI group. The differences between the DI+Vit and control groups according to the MDA levels and the activities of both SOD and CAT were statistically significant. These results suggest that treating rats with a single dose of diazinon increases LPO and some antioxidant enzyme activities in the rat myocardium and, in addition, that single-dose treatment with a combination of vitamins E and C after the administration of diazinon can reduce LPO caused by diazinon, though this treatment was not sufficiently effective to reduce the values to those in control group.     

Impact of Hemidesmus indicus R.Br. extract on ethanol-mediated oxidative damage in rat kidney

The antioxidant effect of the ethanolic extract of Hemidesmus indicus R.Br. root (EHI), an indigenous Ayurvedic medicinal plant in India, was studied in rats with ethanol-induced nephrotoxicity. Administering 5 g/kg body weight/day of ethanol for 60 days to male Wistar rats resulted in significantly elevated levels of serum urea, creatinine and uric acid as well as kidney thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH) and conjugated dienes (CD) as compared to those of the experimental control rats. Decreased levels of kidney superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), vitamin C and vitamin E were also observed on alcohol administration as compared with those of the experimental control rats. EHI was administered at a dose of 500 mg/kg body weight/day for the last 30 days of the experiment to rats with ethanol-induced kidney injury, which significantly decreased the levels of serum urea, uric acid and creatinine as well as kidney TBARS, LOOH and CD and significantly elevated the activities of SOD, CAT, GPx, GSH, vitamin C and vitamin E in kidney as compared to that of untreated ethanol-administered rats. Histopathological observations also correlated with the biochemical parameters. Thus, the data indicate that treatment with EHI offers protection against free radical-mediated oxidative stress in kidney of animals with ethanol-induced nephrotoxicity.     

Age-related changes in antioxidant enzyme activities and lipid peroxidation in lungs of control and sulfur dioxide exposed rats

Antioxidant defenses within the lung are pivotal in preventing damage from oxidative toxicants. There have also been several reports with conflicting results on the antioxidant system during aging. In this study, we attempted to investigate age-related alterations in both antioxidant enzyme activities and thiobarbituric acid-reactive substances (TBARS), a product of lipid peroxidation, in the whole lung of control and sulfur dioxide (SO₂) exposed rats of different age groups (3-, 12-, and 24-months-old). Swiss-Albino Male rats were exposed to 10 ppm SO₂ 1 hr/day, 7 days/week for 6 weeks. The antioxidant enzymes examined include Cu,Zn-superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione S-transferase (GST). A mixed pattern of age-associated alterations in antioxidant activities was observed. SOD, GSH-Px and GST activities were increased with age, but CAT activity was decreased. Lung SOD, GSH-Px and GST activities were also increased in response to SO₂. The level of TBARS was increased with age. SO₂ exposure stimulated lipid peroxide formation in the lung as indicated by an increase in the level of TBARS. These findings suggest that both aging and SO₂ exposure may impose an oxidative stress to the body. We conclude that the increase in the activities of the antioxidant enzymes of the lung during aging, could be interpreted as a positive feedback mechanism in response to rising lipid peroxidation.     

Age-related changes in antioxidant enzyme activities and lipid peroxidation in lungs of control and sulfur dioxide exposed rats

Antioxidant defenses within the lung are pivotal in preventing damage from oxidative toxicants. There have also been several reports with conflicting results on the antioxidant system during aging. In this study, we attempted to investigate age-related alterations in both antioxidant enzyme activities and thiobarbituric acid-reactive substances (TBARS), a product of lipid peroxidation, in the whole lung of control and sulfur dioxide (SO₂) exposed rats of different age groups (3-, 12-, and 24-months-old). Swiss-Albino Male rats were exposed to 10 ppm SO₂ 1 hr/day, 7 days/week for 6 weeks. The antioxidant enzymes examined include Cu,Zn-superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione S-transferase (GST). A mixed pattern of age-associated alterations in antioxidant activities was observed. SOD, GSH-Px and GST activities were increased with age, but CAT activity was decreased. Lung SOD, GSH-Px and GST activities were also increased in response to SO₂. The level of TBARS was increased with age. SO₂ exposure stimulated lipid peroxide formation in the lung as indicated by an increase in the level of TBARS. These findings suggest that both aging and SO₂ exposure may impose an oxidative stress to the body. We conclude that the increase in the activities of the antioxidant enzymes of the lung during aging, could be interpreted as a positive feedback mechanism in response to rising lipid peroxidation.     

Lipid peroxidation and antioxidant status in patients with periodontitis

Our aim was to assess the degree of oxidative stress in patients with periodontitis by measuring their levels of thiobarbituric acid reactive substances (TBARS), enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (GSHPx)), and non-enzymatic antioxidants (vitamins E and C, reduced glutathione (GSH)). This study was conducted on 25 adult chronic periodontitis sufferers who were patients in Rajah Muthiah Dental College and Hospital, Annamalai University. The levels of TBARS and non-enzymatic antioxidants, and the activities of enzymatic antioxidants in the patients' plasma, erythrocytes and gingival tissues were assayed using specific colorimetric methods. The periodontitis sufferers had a significantly higher TBARS level than the healthy subjects. In the plasma, erythrocytes, erythrocyte membranes and gingival tissues of the periodontitis sufferers, enzymatic antioxidant activities were found to be significantly higher, whereas the levels of non-enzymatic antioxidants were significantly lower (except for reduced glutathione in the gingival tissues) relative to the parameters found for healthy subjects. The disturbance in the endogenous antioxidant defense system due to over-production of lipid peroxidation products at inflammatory sites can be related to a higher level of oxidative stress in patients with periodontitis.     

Effect of stress-induced lipid peroxidation on functions of rat peritoneal macrophages

The aim of the present study was to investigate the effects of stress-induced lipid peroxidation on macrophages' functions. Animals were subjected to 4 h immobilization at 4 degrees C in restraining devices. The peritoneal macrophages obtained from rats exposed to cold and restraint stress exhibited an increase in lipid peroxidation and a decline of chemotaxis and phagocytosis compared with control rats. After supplementation with vitamin E, the increment in thiobarbituric acid reactive substances (TBARS) content as the oxidative stress marker and the decline of chemotaxis and phagocytosis in peritoneal macrophages observed during cold-restraint stress was significantly removed. No significant change in catalase activity of peritoneal macrophages was observed in groups exposed to cold-restraint stress and treated with vitamin E. These findings indicate that phagocytic and chemotactic capacities of peritoneal macrophages are decreased by cold-restraint stress and this effect of stress may be related to lipid peroxidation.     

Beneficial effect of combined administration of some naturally occurring antioxidants (vitamins) and thiol chelators in the treatment of chronic lead intoxication

Ameliorative effects of few naturally occurring antioxidants like ascorbic acid (vitamin C), alpha-tocopherol (vitamin E) either alone or in combination with meso-2,3-dimercaptosuccinic acid (DMSA) or monoisoamyl DMSA (MiADMSA), on parameters indicative of oxidative stress in the liver, kidney, brain and blood of lead-exposed rats were studied. Male Wistar rats were exposed to 0.1% lead acetate in drinking water for 3 months and treated thereafter with DMSA or its analogue MiADMSA (50 mg/kg, intraperitoneally), either individually or in combination with vitamin E (5 mg/kg, intramuscularly) or vitamin C (25 mg/kg, orally) once daily for 5 days. The effects of these treatments in influencing the lead-induced alterations in haem synthesis pathway, hepatic, renal and brain oxidative stress and lead concentration from the soft tissues were investigated. Exposure to lead produced a significant inhibition of delta-aminolevulinic acid dehydratase (ALAD) activity from 8.44+/-0.26 in control animals to 1.76+/-0.32 in lead control, reduction in glutathione (GSH) from 3.56+/-0.14 to 2.57+/-0.25 and an increase in zinc protoporphyrin level from 62.0+/-3.9 to 170+/-10.7 in blood, suggesting altered haem synthesis pathway. Both the thiol chelators and the two vitamins were able to increase blood ALAD activity towards normal, however, GSH level responded favorably only to the two thiol chelators. The most prominent effect on blood ALAD activity was, however, observed when MiADMSA was co-administered with vitamin C (7.51+/-0.17). Lead exposure produced a significant depletion of hepatic GSH from 4.59+/-0.78 in control animals to 2.27+/-0.47 in lead controls and catalase activity from 100+/-3.4 to 22.1+/-0.25, while oxidized glutathione (GSSG; 0.34+/-0.05 to 2.05+/-0.25), thiobarbituric acid reactive substance (TBARS; 1.70+/-0.45 to 5.22+/-0.50) and glutathione peroxidase (GPx) levels (3.41+/-0.09 to 6.17+/-0.65) increased significantly, pointing to hepatic oxidative stress. Altered, reduced and oxidized GSH levels showed significant recovery after MiADMSA and DMSA administration while, vitamins E and C were effective in reducing GSSG and TBARS levels and increasing catalase activity. Administration of MiADMSA alone and the combined administration of vitamin C along with DMSA and MiADMSA were most effective in increasing hepatic GSH levels to 4.88+/-0.14, 4.09+/-0.12 and 4.30+/-0.06, respectively. Hepatic catalase also reached near normal level in animals co-administered vitamin C with DMSA or MiADMSA (82.5+/-4.5 and 84.2+/-3.5, respectively). Combined treatments with vitamins and the thiol chelators were also able to effectively reduce lead-induced decrease in renal catalase activity and increase in TBARS and GPx level. Combination therapy, however, was unable to provide an effective reversal in the altered parameters indicative of oxidative stress in different brain regions, except in catalase activity. The result also suggests a beneficial role of vitamin E when administered along with the thiol chelators (particularly with MiADMSA) in reducing body lead burden. Blood lead concentration was reduced from 13.3+/-0.11 in lead control to 0.3+/-0.01 in MiADMSA plus vitamin E-treated rats. Liver and kidney lead concentration also showed a most prominent decrease in MiADMSA plus vitamin E co-administered rats (5.29+/-0.16 to 0.63+/-0.02 and 14.1+/-0.21 to 1.51+/-0.13 in liver and kidney, respectively). These results thus suggest that vitamin C administration during chelation with DMSA/MiADMSA was significantly beneficial in reducing oxidative stress however, it had little or no additive effect on the depletion of lead compared with the effect of chelators alone. Thus, the co-administration of vitamin E during chelation treatment with DMSA or MiADMSA could be recommended for achieving optimum effects of chelation therapy.     

Antiperoxidative and antioxidant effects of Casearia esculenta root extract in streptozotocin-induced diabetic rats

Oxidative stress is currently suggested to play as a pathogenesis in the development of diabetes mellitus. The present study was designed to evaluate the effect of Casearia esculenta root extract on oxidative stress-related parameters in streptozotocin (STZ) -induced diabetic rats. Antidiabetic treatment with C. esculenta root extract (45 days) significantly (p < .05) decreased thiobarbituric acid reactive substances (TBARS) and remarkably improved tissue antioxidants status such as glutathione (GSH), ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) in liver and kidney of STZ-diabetic rats. In diabetics rats, the activities of enzymatic antioxidants such as superoxide dismutase (SOD, EC 1.11.1.1) catalase (CAT, EC 1.11.1.6) were decreased significantly while the activity of glutathione peroxidase (GPx, EC 1.11.1.9) decreased in the liver and increased in the kidney. The treatment of diabetic rats with C. esculenta root extract over a 45-day period returned these levels close to normal. These results suggest that C. esculenta root extracts exhibit antiperoxidative as well as antioxidant effects in STZ-induced diabetic rats.