Aluminium-induced impairment of transcellular calcium absorption in the small intestine: calcium uptake and glutathione influence

Aluminium (Al) has been recognised as a cause of bone tissue disorders. The aims of this work were to investigate: (i) whether Al affects calcium (Ca) entry into enterocyte, and (ii) the possibility that the Al effect upon calbindin-D-related Ca transport would be influenced by intestinal glutathione (GSH) levels. In isolated chicken duodenal enterocytes, 100 microM Al lactate produced a decrease in both, the maximum uptake rate and the affinity constant of 45Ca uptake (CaUPT). This effect of Al on CaUPT was concentration-dependent in the micromolar range, showing an inhibitory saturation type phenomenon which appeared to be higher at pH 6.5 than at pH 7.4, and was not modified by the Ca channel activators A23187 and capsaicin. The simultaneous administration of Al (50 mg elemental Al/kg body weight, as AlCl3) and GSH (10 mmol/kg body weight) to rats during 7 days, prevented the inhibitory effects of Al on Ca transport. The protective effect of GSH was accompanied by an increased duodenal calbindin-D9k expression. Experimental depletion of intestinal GSH by means of D,L-buthionin-[S,R] sulfoximine, a gamma-glutamylcystein-synthase inhibitor, given as a single i.p. dose of 2 mmol/kg body weight, enhanced the degree of reduction of Ca absorption ascribed to Al. Our results suggest that Al might interfere Ca uptake by enterocytes through a general effect on cell membrane, and that an oxidative stress state induced by Al would reduce intestine GSH level affecting calbindin-D function and/or synthesis, thus leading to a reduced transcellular Ca absorption in the small intestine.     

Effect of cadmium and aluminum intake on the antioxidant status and lipid peroxidation in rat tissues.

This work aimed to study the relationship between the accumulation of cadmium (Cd) or aluminum (Al) in certain tissues and the levels of lipid peroxides as well as tissue antioxidants. To carry out such investigations, CdCl2 was given to rats in two dose levels; 0.5 or 2.0 mg/kg i.p for 1 day or daily repeated doses for 2 weeks. Al was given as AlCl3 either in a single dose of 100 mg/kg or daily repeated doses of 20 mg/kg for 2 and 4 weeks. The measured parameters were tissue malondialdehyde (MDA, index of lipid peroxidation) and reduced glutathione (GSH) levels as well as the activities of glutathione peroxidase (GSH-PX), glutathione reductase (GSSG-R), and glucose-6-phosphate dehydrogenase (G-6-PDH) enzymes. Liver and kidney functions were assessed by measuring serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities as well as serum urea and creatinine concentrations. Cd and Al concentrations in the studied tissues were also measured. Results indicated that tissue Cd was significantly increased after administration of either Cd doses. After a single dose of 0.5 or 2.0 mg/kg CdCl2, the increase in tissue Cd levels were accompanied by an increase in MDA and a decrease in GSH levels. On the other hand, after repeated administration of Cd, tissue Cd accumulation was accompanied by increased hepatic and renal GSH levels with decrease in MDA content and a decrease in GSH-PX activity in liver. Liver function was affected at all dose regimens, whereas kidney function was affected only after 2 weeks administration of the higher dose. In Al treated rats, Al concentration was shown to be increased in liver much more than in brain. This was accompanied by a slight decrease in hepatic GSH level after 2 weeks and a decrease in GSH-PX activity after 4 weeks. Liver function was affected only after repeated injection of Al for 2 or 4 weeks. In general, Al administration exhibited safer pattern than Cd.     

Free radical induced increase in protein carbonyl is attenuated by low dose of adenosine in hippocampus and mid brain: implication in neurodegenerative disorders

There is strong evidence that oxidative stress participates in the etiology of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. In the previous studies we have already shown that a combination of alpha-tocopherol and ascorbic acid protect neurons against tert-butyl hydroperoxide (t-BuOOH) induced neurotoxicity in different brain regions including hippocampus and mid brain. In this work, we examined the neuroprotective effect of low dose of adenosine against protein oxidation (protein carbonyls) in parallel with the level of reduced glutathione (GSH) in hippocampus and mid brain regions of mouse brain. The t-BuOOH was injected intraperitoneally in three concentrations (50, 100, 150 mg/kg b.w.) for 10 days. Results showed dose dependent increase in protein carbonyl (PC) in hippocampus and mid brain region. This increase was accompanied by a significant (p < 0.05) decline in GSH content in both brain regions of t-BuOOH treated mice. Adenosine (1 mg/kg b.w.) protected both hippocampus and mid brain neurons against protein oxidation as evidenced by reduction in protein carbonyl content. The GSH content was significantly (p < 0.05) increased after the treatment of adenosine in both brain regions. These data show that prior treatment with low dose of adenosine attenuates the oxidative protein damage with parallel increase in the GSH level in hippocampus and mid brain of t-BuOOH induced mice.     

Excess of glucocorticoids impairs whole-body antioxidant status in young rats. relation to the effect of dexamethasone in soleus muscle and spleen.

The action of glucocorticoids in high doses is catabolic, but not much is known about the accompanying effects on antioxidative capacity of the entire body. Animals were treated (or not) with dexamethasone (Dex) 2 mg/kg b.w. d-1 during 5 consecutive days followed by recovery, during which an additional group received 3-hydroxy-3-methylbutyrate (40 mg/kg b.w.). Animals were killed after treatment with Dex, and after 5 days of the recovery period. Dexamethasone treatment decreased appetite almost twofold (from 20 g/day to 10 g/day, P < 0.001). Feed restriction, however, seemed to have only minor impact on the effects observed since body weight loss of pair-fed rats after the 5th day of treatment was only 2% and Dex-treated rats decrease in body weight was 22% (P < 0.05). In turn, wet weight of the soleus muscle (expressed per body weight) did not significantly decrease after Dex treatment, suggesting relative resistance of oxidative type muscles to the catabolic action of dexamethasone. Spleen wet weight expressed per body weight dropped by 65% (P<0.001). Additionally, there was a 46% reduction (P<0.001) of blood glutathione (GSH/Hb), and 36% (P < 0.001) of muscle glutathione (GSH/tissue wet weight). This suggests that dexamethasone directly and/or indirectly impaired antioxidant reactions. This was further confirmed by a significant (49%) decline of SOD-1 activity in erythrocytes isolated from the group treated with dexamethasone. Another index of lipid peroxidation (TBARS) was also significantly increased. Activity of blood plasma CK increased by 73% (P<0.001) in Dex-treated rats, indicating moderate injury of muscle tissue. In conclusion, young growing rats were sensitive to the dosage of dexamethasone, but in contrast to lymphoid tissue, could easily compensate the outcomes of impaired antioxidative defence within 5 days of recovery.     

Chemoprotective activity of an extract of Phyllanthus amarus against cyclophosphamide induced toxicity in mice.

The effect of 75% methanolic extract of the plant Phyllanthus amarus (P. amarus) was studied against cyclophosphamide (CTX) induced toxicity in mice. Administration of CTX (25 mg/kg b.wt, i.p.) for 14 days produced significant myelosuppression as seen from the decreased WBC count and bone marrow cellularity. Administration of P. amarus extract at doses 250 and 750 mg/kg b.wt significantly reduced the myelosuppression and improved the WBC count, bone marrow cellularity as well as the number of maturing monocytes. CTX treatment also reduced the activity of glutathione system and increased the activity of phase I enzyme that metabolize CTX to its toxic side products. P. amarus administration was found to decrease the activity of phase I enzyme. Administration of P. amarus also increased the cellular glutathione (GSH) and glutathione-S-transferase (GST), thereby decreasing the effect of toxic metabolites of CTX on the cells. Administration of P. amarus did not reduce the tumor reducing activity of CTX. In fact, there was a synergistic action of CTX and P. amarus in reducing the solid tumors in mice. Results indicated that administration of P. amarus can significantly reduce the toxic side effects of CTX and is not interfering with the antitumor efficiency of CTX.     

Effects of a root-colonized dark septate endophyte on the glutathione metabolism in maize plants under cadmium stress

A high Cd-tolerant dark septate endophyte (DSE), Exophiala pisciphila, was inoculated into maize (Zea mays L.) roots under Cd stress. The Cd content, enzymes activity and thiol compound content relevant to glutathione (GSH) metabolism in maize leaves were analyzed. The Cd content in maize shoots increased with increasing Cd stress, but the DSE significantly reduced the Cd content at the 40?mg/kg Cd treatment. Cd stress increased the enzyme activity of glutathione reductase (GR), glutathione S-transferase (GST) and glutathione peroxidase (GSH-Px) as well as the thiol compound contents of sulfur, thiols (-SH) and oxidized glutathione (GSSG). The content of reduced GSH and the GSH/GSSG ratio reached a peak at the 5?mg/kg Cd treatment but then decreased with increasing Cd stress. Furthermore, the DSE significantly enhanced the GR and GSH-Px activity and increased the contents of -SH and GSH under low Cd stress (5 and 10?mg/kg), but decreased the γ-glutamylcysteine synthetase and GST activity under high Cd stress (20 and 40?mg/kg). Highly positive correlations between the Cd content with enzymes activity and enzymes activity with thiol compound content were observed. Results indicated that DSE played a role in activating GSH metabolism in maize leaves under Cd stress.     

Garlic and vitamin E provides antioxidant defence in tissues of female rats treated with nicotine

Nicotine is known to induce oxidative stress in rat tissues and the antioxidant properties of garlic have been reported. This study was designed to determine if the peroxidative damage caused by nicotine administration can be effectively prevented with garlic juice, and vitamin E, a known antioxidant.Four groups of six rats each were divided into: Group I: (control) received 0.2ml of 0.9% normal saline, group II (received nicotine 0.6mg/kg b.w subcutaneously), group III (received nicotine 0.6mg/kg b.w + garlic juice 100mg/kg b.w orally), and group IV (received nicotine 0.6mg/kg b.w + Vitamin E 100mg/kg b.w orally). All animals were treated for 21 days. The pituitary gland, ovary, uterus, heart, liver and kidney of the animals were harvested, weighed and homogenized. Malondialdehyde (MDA), superoxide dismutase (SOD) and reduced glutathione (GSH) were then measured.Concentration of MDA was significantly increased in tissues of nicotine treated rats when compared with the control. In group III and IV, MDA levels were significantly reduced when compared with nicotine group. The activities of SOD and GSH significantly decreased in group II (nicotine only) rat tissues, while it was significantly increased in group III and IV rat tissues. The study showed that garlic juice extract (100mg/kg b.w) and vitamin E (100mg/kg b.w) administration prevented oxidative damage in rat tissues treated with nicotine. The study also showed that vitamin E has a more potent antioxidant activity than garlic juice in preventing nicotine induced oxidative damage in rat. Keywords: Nicotine, Vitamin E, Garlic, antioxidant.     

The Effects of Glutamate and Citrate on Absorption and Distribution of Aluminum in Rats

The objective of this study was to evaluate the effect of glutamate (Glu) and citrate (Cit) on the absorption and distribution of aluminum in rats. In the in vitro experiment, 18 adult male Sprague-Dawley rats (average weight of 250 ± 15 g) were randomly divided into three groups. The entire intestine was rapidly removed and cultured in prediction samples of 20 mmol AlCl(3), 20 mmol AlCl(3)+20 mmol Cit, and 20 mmol AlCl(3)+20 mmol Glu, respectively. Liquid in different intestines and the intestines were obtained for Al determination. In the in vivo chronic study, 24 adult male Sprague-Dawley rats (average weight of 127 ± 10 g) were divided into four groups fed with the following diets: no Al and Glu added (control), AlCl(3) (1.2 mmol), AlCl(3) (1.2 mmol) + Cit (1.2 mmol), and AlCl(3) (1.2 mmol) + Glu (1.2 mmol) daily for 50 days, respectively. After rat sacrifice, blood samples were obtained for biochemical analyses, and organ samples like the brain, kidney, liver, and bone were rapidly taken for Al determination. The results showed that the absorption rate of Al with the following order: duodenum > jejunum > ileum in the in vitro study and the administration of AlCl(3)+Cit or AlCl(3)+Glu resulted in significant increases in Al absorption in the three parts of the gut (duodenum, jejunum, and ileum) compared to the AlCl(3) alone group based on wet weight (P < 0.05). There were no differences between the AlCl(3)+Cit and AlCl(3)+Glu groups. In the in vivo chronic study, supplementing either AlCl(3) alone or AlCl(3)+Glu decreased food consumption significantly (P < 0.05) compared with the control group. Compared with the control group, animals fed with the AlCl(3) diet monitored for red blood cell, kidney, and liver showed a higher level (P < 0.05), but did not significantly increase Al retention in the brain and bone (P > 0.05); animals fed with AlCl(3)+Cit diets were monitored for higher Al retention in the brain, kidney, bone, and liver (P < 0.05), while animals fed with AlCl(3)+Glu diets were monitored for red blood cell, brain, and kidney (P < 0.05). Compared with the AlCl(3) group, simultaneous administration of AlCl(3) and Glu led to a significant increase in Al retention in red blood cell, brain, and kidney (P < 0.01) while AlCl(3) and Cit in the kidney and bone (P < 0.01). Simultaneous administration of AlCl(3) and Cit significantly increases plasma malondialdehyde level (P < 0.05); both simultaneous administration of AlCl(3) and Glu or AlCl(3) and Cit led to significant decreases in superoxide dismutase level in the plasma (P < 0.05), while AlCl3 alone did not. The results indicated that both Cit and Glu enhanced Al absorption in the intestine in vitro, and Glu increased Al deposition in red blood cell, brain, and kidney in vivo.     

The role of the glutathione system in seizures induced by diphenyl diselenide in rat pups

The present study investigated the role of the glutathione system in seizures induced by diphenyl diselenide (PhSe)₂ (50 mg/kg) in rat pups (post natal day, 12–14). Reduced glutathione (GSH) (300 nmol/site; i.c.v.), administered 20 min before (PhSe)₂, abolished the appearance of seizures, protected against the inhibition of catalase and δ-aminolevulinic dehydratase (δ-ALA-D) activities and increased glutathione peroxidase (GPx) activity induced by (PhSe)₂. Administration of l-buthionine sulfoximine (BSO, a GSH-depleting compound) (3.2 μmol/site; i.c.v.) 24 h before (PhSe)₂ increased the percentage (42–100%) of rat pups which had seizure episodes, reduced the onset for the first convulsive episode. In addition, BSO increased thiobarbituric acid reactive species (TBARS) levels and decreased GSH content, catalase, δ-ALA-D and Na⁺, K⁺-ATPase activities. Treatment with sub effective doses of GSH (10 nmol/site) and d-2-amino-7-phosphonoheptanoic acid (AP-7, an antagonist of the glutamate site at the NMDA receptor; 5 mg/kg, i.p.) abolished the appearance of seizures induced by (PhSe)₂ in rat pups. Sub effective doses of GSH and kynurenic acid (an antagonist of strychnine-insensitive glycine site at the NMDA receptor; 40 mg/kg, i.p.) were also able in abolishing the appearance of seizures induced by (PhSe)₂. In conclusion, administration of GSH protected against seizure episodes induced by (PhSe)₂ in rat pups by reducing oxidative stress and, at least in part, by acting as an antagonist of glutamate and glycine modulatory sites in the NMDA receptor.     

饲料中添加谷胱甘肽对黄颡鱼幼鱼组织谷胱甘肽含量、免疫及抗氧化性能的影响

研究旨在探讨饲料中添加还原型谷胱甘肽(Glutathione, GSH)对黄颡鱼幼鱼(Pelteobagrus fulvidraco)组织谷胱甘肽含量、免疫及抗氧化性能的影响。选用初始体重为(1.32±0.01) g的黄颡鱼800尾, 随机分为5组, 每组4个重复, 每个重复40 尾鱼, 分别投喂基础饲料和添加100、300、500和700 mg/kg GSH的试验饲料, 饲养56d后采样分析, 并采用氯化铵进行96h氨氮应激试验。结果表明: 除100 mg/kg组外, 饲料中添加GSH显著提高黄颡鱼肝脏、血清GSH含量(P<0.05), 当GSH添加量≥300 mg/kg时, 肝脏和血清GSH含量均呈现稳定状态。随着饲料中谷胱甘肽水平的增加, 血清免疫和肝脏抗氧化指标均呈现先升高后降低的趋势, 其中300和500 mg/kg组溶菌酶与碱性磷酸酶活性、300 mg/kg组免疫球蛋白M与补体4含量、500 mg/kg组酸性磷酸酶活性与对照组相比显著升高(P<0.05)。与对照组和700 mg/kg组相比, 300 mg/kg组肝脏超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化酶活性和总抗氧化能力与血清超氧化物歧化酶、谷胱甘肽过氧化酶活性均显著高升高(P<0.05); 且300 mg/kg组血清丙二醛含量显著降低(P<0.05)。氨氮应激96h时, 与对照组相比, 300 mg/kg组肝脏和血清超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化酶活性力均显著升高(P<0.05), 且300 mg/kg组血清丙二醛含量显著降低(P<0.05)。由此可见, 饲料中添加谷胱甘肽能提高黄颡鱼幼鱼组织谷胱甘肽含量、免疫及抗氧化性能, 其中以300—500 mg/kg为宜。     

Bilirubin clearance and antioxidant activities of ethanol extract of Phyllanthus amarus root in phenylhydrazine-induced neonatal jaundice in mice

The ability of ethanol extract of Phyllanthus amarus root (EEPA) to decrease bilirubin level and oxidative stress in phenylhydrazine-induced neonatal jaundice in mice was investigated. Administration of phenylhydrazine (75 mg/kg b.w.) significantly elevated total and unconjugated serum bilirubin level compared to control mice. EEPA (5, 10, and 20 mg/kg b.w., oral) dose-dependently reduced the bilirubin level. EEPA treatment also upregulated hepatic CAR and CYP3A1, accounting for its ability to facilitate bilirubin clearance. A single dose of EEPA (20 mg/kg b.w.) induced higher level of bilirubin clearance than phototherapy, widely used for treating neonatal jaundice. Furthermore, phenylhydrazine administration significantly increased MDA, protein carbonyl, and total thiol content and lowered the GSH level along with superoxide dismutase and catalase activity in erythrocyte compared to the control group. Single administration of EEPA (20 mg/kg b.w.) significantly reversed the trend. Presence of gallic acid, gentisic acid, and ortho-coumaric acid in EEPA was identified by HPLC analysis. Amongst these, the major phenolic constituent, gallic acid, exhibited significant bilirubin-lowering effect. These results suggested that P. amarus may be beneficial in reducing bilirubin level as well as oxidative stress in neonatal jaundice.     

Antioxidative effect of ursodeoxycholic acid in the liver of rats with oxidative stress caused by gamma-irradiation

We studied effects of ursodeoxycholic acid (UDCA) (10 and 100 mg/kg b.w.) on the free radical generation, lipid peroxidation and the antioxidant defense system in the liver of rats with oxidative stress caused by gamma-irradiation. Both doses of UDCA normalized the liver parameters enhanced by gamma-irradiation: the content of superoxide anion and carbonyl-containing products of lipid peroxidation (alkanals, alkenals, alkadienals and ketones), the superoxide dismutase activity and the chemiluminescence enhanced by luminol. Only the highest dose of UDCA (100 mg/kg b.w.) decreased the chemiluminescence enhanced by lucigenin in liver microsomes and the hydroxyalkenals content in the liver. UDCA prevented reduced glutathione depletion caused by gamma-irradiation, whereas glutathione-related enzyme activities did not change under the influence of both the UDCA doses as well as gamma-irradiation. Thus, the data obtained suggest that UDCA is a metabolite having the sufficiently effective antioxidant properties.     

Modulatory influence of dietary resveratrol during different phases of 1,2-dimethylhydrazine induced mucosal lipid-peroxidation, antioxidant status and aberrant crypt foci development in rat colon carcinogenesis

To shed light on the association of lipid peroxidation and antioxidant status with the development of aberrant crypt foci (ACF), we studied the modulatory influence of resveratrol, supplemented in three dietary regimens (initiation, post-initiation and entire period) on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. Rats were administered DMH (20 mg/kg body weight, s.c.) for 15 weeks and were supplemented with resveratrol (8 mg/kg body weight, p.o. everyday) in three dietary regimens. Intestines and colons were analyzed for the levels of diene conjugates (DC), lipid hydroperoxides (LOOHs) and thiobarbituric acid reactive substances (TBARS). Enzymic antioxidants (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GPX; glutathione S-transferase, GST; and glutathione reductase, GR) and non-enzymic reserve (reduced glutathione, GSH; ascorbate; and alpha-tocopherol) were also assessed in the intestine and colon. Unsupplemented DMH exposed rats showed significantly decreased levels/activities of tissue DC, LOOHs, TBARS, SOD, CAT, GSH, GR and significantly elevated (P<0.05) GPX, GST, alpha-tocopherol and ascorbate as compared to control rats. Resveratrol supplementation during the entire period of the study resulted in significant (P<0.01) modulation of lipid peroxidation markers and antioxidants status, which were paralleled with ACF suppression, as compared to DMH-alone treated rats. These results indicate that resveratrol effectively inhibits DMH-induced ACF and colonic tumor development.     

Molecular and biochemical investigations on the effect of quercetin on oxidative stress induced by cisplatin in rat kidney

The present study was aimed to investigate the ability of quercetin (QE) to ameliorate adverse effects of cisplatin (Cis.) on the renal tissue antioxidants by investigating the kidney antioxidant gene expression and the antioxidant enzymes activity. Forty rats divided into. Control rats. QE treated rats were orally administered 100 mg QE/kg for successive 30 days. Cis. injected rats were administered i.p. Cis. (12 mg/kg b.w.) for 5 mutual days. Cis. + QE rats were administered Cis. i.p. (12 mg/kg) and orally administered 100 mg QE/kg for consecutive 30 days. The obtained results indicated that Cis. induced oxidative stress in the renal tissue. That was through induction of free radical production, inhibition of the activity of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) as well their genes expression. At the same time, vitamin E, vitamin C and reduced glutathione (GSH) levels were decreased. QE had the ability to overcome cisplatin-induced oxidative stress through the reduction of free radical levels. The antioxidant genes expression and antioxidant enzymes activity were induced. Finally the vitamin E, vitamin C and GSH levels were increased. Our work, proved the renoprotective effects of QE against oxidative stress induced by cisplatin.     

Effects of zinc pre-treatment on blood glutathione,serum zinc and kidney histological organisation in male rats exposed to cadmium

The effects of sub-chronic exposure to cadmium (Cd) on the blood glutathione, serum zinc and on the kidney histological organisation in rats as well as the possible protective role of zinc (Zn) are the object of this study. For this purpose, 60 male Wistar rats (8 weeks old) were divided into three groups: the first group was exposed to Cd in the form of CdCl₂, administered in five doses (each of 0.4 mg Cd/kg b.w.) on days 5, 10, 15, 20 and 25, giving a total dose of 2 mg Cd/kg b.w., i.p.; the second group was simultaneously exposed to Zn and Cd with the same timeline and the same doses of Cd as the first group but with, in addition, injections of Zn in the form of ZnCl₂, administered in doses of 0.8 mg Zn/kg b.w., giving a total dose of 4 mg Zn/kg b w, i.p.; a control group received 0.5 mL of physiological saline in an identical manner. Intoxication with Cd was followed by a significant decrease in blood glutathione, increase in oxidized glutathione as well as histological damage in kidneys. Pre-treatment with Zn exhibited a protective role against Cd toxicity with a significant decrease in serum zinc content. This fact may be explained by an excessive use of zinc in metallothionein synthesis as a cadmium detoxification agent.     

Effect of cadmium on lipid peroxidation and activities of antioxidant enzymes in growing pigs

Malondialdehyde (MDA), glutathione (GSH) content, total antioxidant capacity (T-AOC) levels, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione transferase (GST) activities were studied in serum, liver, and kidney of growing pigs after graded doses of cadmium administration in diets. One hundred ninety-two barrows (Duroc x Landrace x Yorkshire), with similar initial body weight 27.67±1.33 kg, were randomly allotted into 4 different treatments with 3 replications (16 pigs per replication). The treatments received the same basal diet added with 0, 0.5, 5.0, and 10.0 mg/kg cadmium (as CdCl₂), respectively. The results showed pigs treated with 10 mg/kg cadmium significantly decreased average daily gain (ADG) (p<0.05) and increased feed/gain ratio (F/G) (p<0.05) compared to the control. In this treatment, the contents of MDA increased significantly (p<0.05), GSH concentrations, T-AOC levels, and the activities of SOD, GSH-PX, and GST decreased significantly (p<0.05). The results indicate 10 mg/kg cadmium could decrease pig antioxidant capacity after extended exposure and cadmium-induced increase lipid peroxidation might not be only the result of the possibility of lower level of GSH but could also be as a result of direct action of cadmium on peroxidation reaction.     

N-acetylcysteine enhances muscle cysteine and glutathione availability and attenuates fatigue during prolonged exercise in endurance-trained individuals.

The production of reactive oxygen species in skeletal muscle is linked with muscle fatigue. This study investigated the effects of the antioxidant compound N-acetylcysteine (NAC) on muscle cysteine, cystine, and glutathione and on time to fatigue during prolonged, submaximal exercise in endurance athletes. Eight men completed a double-blind, crossover study, receiving NAC or placebo before and during cycling for 45 min at 71% peak oxygen consumption (VO2 peak) and then to fatigue at 92% VO2 peak. NAC was intravenously infused at 125 mg.kg(-1).h(-1) for 15 min and then at 25 mg.kg(-1).h(-1) for 20 min before and throughout exercise. Arterialized venous blood was analyzed for NAC, glutathione status, and cysteine concentration. A vastus lateralis biopsy was taken preinfusion, at 45 min of exercise, and at fatigue and was analyzed for NAC, total glutathione (TGSH), reduced glutathione (GSH), cysteine, and cystine. Time to fatigue at 92% VO2 peak was reproducible in preliminary trials (coefficient of variation 5.6 +/- 0.6%) and with NAC was enhanced by 26.3 +/- 9.1% (NAC 6.4 +/- 0.6 min vs. Con 5.3 +/- 0.7 min; P <0.05). NAC increased muscle total and reduced NAC at both 45 min and fatigue (P <0.005). Muscle cysteine and cystine were unchanged during Con, but were elevated above preinfusion levels with NAC (P <0.001). Muscle TGSH (P <0.05) declined and muscle GSH tended to decline (P=0.06) during exercise. Both were greater with NAC (P <0.05). Neither exercise nor NAC affected whole blood TGSH. Whereas blood GSH was decreased and calculated oxidized glutathione increased with exercise (P <0.05), both were unaffected by NAC. In conclusion, NAC improved performance in well-trained individuals, with enhanced muscle cysteine and GSH availability a likely mechanism.     

Role of combined administration of Tiron and glutathione against aluminum-induced oxidative stress in rat brain.

The current study was carried out to investigate the potential role of 4,5 dihydroxy benzene 1,3 disulfonic acid di sodium salt (Tiron) and glutathione (GSH) either individually or in combination against aluminum (Al)-induced toxicity in Wistar rats. Animals were exposed to aluminum chloride at a dose of 172.5mg/kg/d orally for 10 weeks. Tiron and GSH were administered at a dose of 471-mg/kg/d i.p. and 100mg/kg/d orally, respectively, for 7 consecutive days. Tiron is a diphenolic chelating compound which forms water soluble complexes with a large number of metal ions. Induction of oxidative stress was recorded in brain and serum after Al exposure. Significant decrease was recorded in reduced glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GP(x)), catalase (CAT), superoxide dismutase (SOD), acetyl cholinesterase (AChE) and an increase was observed in thiobarbituric acid reacting substance (TBARS) and glutathione-S-transferase (GST) in brain and serum. Most of the above parameters responded positively to individual therapy with Tiron, but more pronounced beneficial effects on the above-described parameters were observed when Tiron was administered in combination with GSH. Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) studies also showed significantly high concentration of Al in brain and blood. Tiron was slightly more effective then GSH in reducing the concentration of Al from the brain and blood, however, no further improvement was recorded when Tiron was administered in combination with GSH in reducing the concentration of Al.     

Pro-oxidant activity of aluminum in the rat hippocampus: gene expression of antioxidant enzymes after melatonin administration

Aluminum (Al)-induced pro-oxidant activity and the protective role of exogenous melatonin, as well as the mRNA levels of some antioxidant enzymes, were determined in the hippocampi of rats following administration of Al and/or melatonin. Two groups of male rats were intraperitoneally injected with Al (as Al lactate) or melatonin only, at doses of 7 and 10 mg/kg/day, respectively, for 11 weeks. During this period, a third group of animals received Al (7 mg/kg/day) plus melatonin (10 mg/kg/day). At the end of the treatment, hippocampus was removed and processed to examine the following oxidative stress markers: glutathione transferase (GST), reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), thiobarbituric acid reactive substances (TBARS), as well as protein content. Gene expression of Cu-ZnSOD, MnSOD, GPx, and CAT was evaluated by real-time RT-PCR. On the other hand, Al, Fe, Mn, Cu, and Zn concentrations in hippocampus were also determined. The results show that Al exposure promotes oxidative stress in the rat hippocampus, with an increase in Al concentrations. The biochemical changes observed in this tissue indicate that Al acts as pro-oxidant agent, while melatonin exerts antioxidant action by increasing the mRNA levels of the antioxidant enzymes evaluated. The protective effects of melatonin, together with its low toxicity and its capacity to increase mRNA levels of antioxidant enzymes, suggest that this hormone might be administered as a potential supplement in the treatment of neurological disorders in which oxidative stress is involved.     

The modulatory influence of p-methoxycinnamic acid, an active rice bran phenolic acid, against 1,2-dimethylhydrazine-induced lipid peroxidation, antioxidant status and aberrant crypt foci in rat colon carcinogenesis

We investigated the chemopreventive effect of p-methoxycinnamic acid (p-MCA), an active phenolic acid of rice bran, turmeric, and Kaemperfia galanga against 1,2-dimethylhydrazine-induced rat colon carcinogenesis. Male albino Wistar rats were randomly divided into six groups. Group 1 consisted of control rats that received a modified pellet diet and 0.1% carboxymethyl cellulose. The rats in Group 2 received a modified pellet diet supplemented with p-MCA [80 mg/kg body weight (b.wt.) post-orally (p.o.)] everyday. The rats in Groups 3-6 received 1,2-dimethylhydrazine (DMH) (20 mg/kg b.wt.) via subcutaneous injections once a week for the first 4 weeks; additionally, the rats in Groups 4, 5 and 6 received p-MCA at doses of 20, 40 and 80 mg/kg b.wt./day p.o., respectively, everyday for 16 weeks. The rats were sacrificed at the end of the experimental period of 16 weeks. The DMH-treated rats exhibited an increased incidence of aberrant crypt foci (ACF) development; an increased crypt multiplicity; decreased concentrations of tissue lipid peroxidation markers such as thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and lipid hydroperoxides (LOOH); decreased levels of tissue enzymic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR); and decreased levels of non-enzymic antioxidants such as reduced glutathione (GSH) and vitamins C, E and A in the colon. Supplementation with p-MCA significantly reversed these changes and significantly inhibited the formation of ACF and its multiplicity. Thus, our findings demonstrate that p-MCA exerts a strong chemopreventive activity against 1,2-dimethylhydrazine-induced colon carcinogenesis by virtue of its ability to prevent the alterations in DMH-induced circulatory and tissue oxidative stress and preneoplastic changes. p-MCA was more effective when administered at a dose of 40 mg/kg b.wt. than at the other two doses tested.