Total and Mitochondrial Nitrosative Stress,Decreased Brain-Derived Neurotrophic Factor (BDNF) Levels and Glutamate Uptake,and Evidence of Endoplasmic Reticulum Stress in the Hippocampus of Vitamin A-Treated Rats

Vitamin A supplementation has caused concern among public health researchers due to its ability in decreasing life quality from acute toxicological effects to increasing mortality rates among vitamin supplement users. For example, it was described cognitive decline (i.e. irritability, anxiety, and depression) in patients subjected to long-term vitamin A therapy, as occurs in cancer treatment. However, the mechanism by which vitamin A affects mammalian cognition is not completely understood. Then, we performed the present work to investigate the effects of vitamin A supplementation at clinical doses (1,000–9,000 IU/kg day⁻¹) for 28 days on rat hippocampal nitrosative stress levels (both total and mitochondrial), bioenergetics states, brain-derived neurotrophic factor (BDNF), alpha- and beta-synucleins, BiP and dopamine receptor 2 (D2 receptor) contents, and glutamate uptake. We observed mitochondrial impairment regarding respiratory chain function: increased complex I-III, but decreased complex IV enzyme activity. Also, decreased BDNF levels were observed in vitamin A-treated rats. The present data demonstrates, at least in part, that mitochondrial dysfunction and decreased BDNF and D2 receptors levels, as well as decreased glutamate uptake may take an important role in the mechanism behind the previously reported cognitive disturbances associated to vitamin A supplementation.     

Acute and Chronic Hyperammonemia Modulate Antioxidant Enzymes Differently in Cerebral Cortex and Cerebellum

Studies on acute hyperammonemic models suggest a role of oxidative stress in neuropathology of ammonia toxicity. Mostly, a low grade chronic type hyperammonemia (HA) prevails in patients with liver diseases and causes derangements mainly in cerebellum associated functions. To understand whether cerebellum responds differently than other brain regions to chronic type HA with respect to oxidative stress, this article compares active levels of all the antioxidant enzymes vis a vis extent of oxidative damage in cerebral cortex and cerebellum of rats with acute and chronic HA induced by intra-peritoneal injection of ammonium acetate (successive doses of 10 × 10³ & 8 × 10³ μmol/kg b.w. at 30 min interval for acute and 8 × 10³ μmol/kg b.w. daily up to 3 days for chronic HA). As compared to the respective control sets, cerebral cortex of acute HA rats showed significant decline (P < 0.01–0.001) in the levels of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) but with no change in glutathione reductase (GR). In cerebellum of acute HA rats, SOD, catalase and GR though declined significantly, GPx level was found to be stable. Contrary to this, during chronic HA, levels of SOD, catalase and GPx increased significantly in cerebral cortex, however, with a significant decline in the levels of SOD and GPx in cerebellum. The results suggest that most of the antioxidant enzymes decline during acute HA in both the brain regions. However, chronic HA induces adaptive changes, with respect to the critical antioxidant enzymes, in cerebral cortex and renders cerebellum susceptible to the oxidative stress. This is supported by ∼ 2- and 3-times increases in the level of lipid peroxidation in cerebellum during chronic and acute HA respectively, however, with no change in the cortex due to chronic HA.     

Vitamin A supplementation at pharmacological doses induces nitrosative stress on the hypothalamus of adult Wistar rats

Vitamin A is a micronutrient involved in the regulation of a normal mammalian brain function. In spite of this, it has been demonstrated that vitamin A exerts a wide range of deleterious effects regarding neuronal homeostasis, for instance impairing brain metabolism and suppressing neurogenesis, to cite a few. In addition, vitamin A is a redox active molecule, i.e. it is both anti- and pro-oxidant, depending on its concentration. In the herein presented work, we performed some experiments aiming to investigate the effects of clinically applied doses of vitamin A (1000–9000 IU/kg/day during 28 days) on rat hypothalamic redox state and mitochondrial electron transfer chain (METC) activity, as well as on hypothalamic α-synuclein and D2 receptor (dopamine receptor) contents. Additionally, we quantified caspase-3 activity and tumor necrosis factor-α (TNF-α) levels to assess either neuronal death or an inflammatory state in such brain area. We found that vitamin A supplementation increased free radical production, as well as oxidative and nitrosative stress, in rat hypothalamus. Also, we observed increased complex I-III activity, but decreased complex IV activity in the hypothalamus of vitamin A-treated rats, which may give rise to the increased superoxide anion (O₂⁻) production found here. Other parameters investigated here, i.e. α-synuclein and D2 receptor contents did not change. Even though we did not observe signs of increased cell death or inflammation in the rat hypothalamus, more attention is needed when vitamin A is the choice of treatment in certain pathologies.     

Differential expression of SLC30A10 and RAGE in mouse pups by early life lead exposure

BackgroundSLC30A10 and RAGE are widely recognized as pivotal regulators of Aβ plaque transport and accumulation. Prior investigations have established a link between early lead exposure and cerebral harm in offspring, attributable to Aβ buildup and amyloid plaque deposition. However, the impact of lead on the protein expression of SLC30A10 and RAGE has yet to be elucidated. This study seeks to confirm the influence of maternal lead exposure during pregnancy, specifically through lead-containing drinking water, on the protein expression of SLC30A10 and RAGE in mice offspring. Furthermore, this research aims to provide further evidence of lead-induced neurotoxicity.MethodsFour cohorts of mice were subjected to lead exposure at concentrations of 0 mM, 0.25 mM, 0.5 mM, and 1 mM over a period of 42 uninterrupted days, spanning from pregnancy to the weaning phase. On postnatal day 21, the offspring mice underwent assessments. The levels of lead in the blood, hippocampus, and cerebral cortex were scrutinized, while the mice's cognitive abilities pertaining to learning and memory were probed through the utilization of the Morris water maze. Furthermore, Western blotting and immunofluorescence techniques were employed to analyze the expression levels of SLC30A10 and RAGE in the hippocampus and cerebral cortex.ResultsThe findings revealed a significant elevation in lead concentration within the brains and bloodstreams of mice, mirroring the increased lead exposure experienced by their mothers during the designated period (P < 0.05). Notably, in the Morris water maze assessment, the lead-exposed group exhibited noticeably diminished spatial memory compared to the control group (P < 0.05). Both immunofluorescence and Western blot analyses effectively demonstrated the concomitant impact of varying lead exposure levels on the hippocampal and cerebral cortex regions of the offspring. The expression levels of SLC30A10 displayed a negative correlation with lead doses (P < 0.05). Surprisingly, under identical circumstances, the expression of RAGE in the hippocampus and cortex of the offspring exhibited a positive correlation with lead doses (P < 0.05).ConclusionSLC30A10 potentially exerts distinct influence on exacerbated Aβ accumulation and transportation in contrast to RAGE. Disparities in brain expression of RAGE and SLC30A10 may contribute to the neurotoxic effects induced by lead.     

Acamprosate Modulates Alcohol-Induced Hippocampal NMDA Receptors and Brain Microsomal Ca2+-ATPase but Induces Oxidative Stress in Rat

We investigated the effects of acamprosate on alcohol-induced oxidative toxicity, microsomal membrane Ca²⁺-ATPase (MMCA) activity and N-methyl-d-aspartate receptor (NMDAR) subunits in rat brain. Forty male rats were equally divided into four groups. The first group was used as control, and the second group received ethanol. Acamprosate and acamprosate plus ethanol each day were administered to rats constituting the third and fourth groups for 21 days, respectively. Brain cortical and hippocampal samples were taken from the four groups after 21 days. Brain cortical lipid peroxidation (LP) levels and MMCA activity were higher in the alcohol group than in control, although glutathione peroxidase (GSH-Px), vitamin C, vitamin E and β-carotene values were lower in the alcohol group than in control. LP levels were further increased in the acamprosate and alcohol + acamprosate groups compared with the alcohol group. GSH-Px, vitamin A, vitamin C, vitamin E and β-carotene in the acamprosate and alcohol + acamprosate groups were further decreased compared with the alcohol group. Hippocampal NMDAR 2A and 2B subunit concentrations were lower in the alcohol group than in control, although they were increased by acamprosate and alcohol + acamprosate. Brain cortical MMCA activity was higher in the acamprosate group than in the alcohol-treated rats, although its activity was lower in the alcohol + acamprosate group than in the acamprosate group. Brain cortical reduced glutathione levels were not found to be statistically different in any of the groups. Oxidative stress has been proposed to explain the biological side effects of experimental alcohol intake. Acamprosate and alcohol-induced oxidative stress decreased brain antioxidant vitamins in the alcoholic rats.     

Antioxidants prevent memory deficits provoked by chronic variable stress in rats

Learning and memory deficits occur in depression and other stress related disorders. Although the pathogenesis of cognitive impairment after stress has not been fully elucidated, factors such as oxidative stress and neurotrophins are thought to play possible roles. Here we investigated the effect of treatment with vitamin E (40 mg/kg) and vitamin C (100 mg/kg) on the effects elicited by chronic variable stress on rat performance in Morris water maze. Brain-derived neurotrophic factor (BDNF) immunocontent was also evaluated in hippocampus of rats. Sixty-day old Wistar rats were submitted to different stressors for 40 days (stressed group). Half of stressed group received administration of vitamins once a day, during the period of stress. Chronically stressed rats presented a marked decrease in reference memory in the water maze task as well as a reduced efficiency to find the platform in the working memory task. Rats treated with vitamins E and C had part of the above effects prevented, suggesting the participation of oxidative stress in such effects. The BDNF levels were not altered in hippocampus of stressed group when compared to controls. Our findings lend support to a novel therapeutic strategy, associated with these vitamins, to the cognitive dysfunction observed in depression and other stress related diseases.     

Vitamin A supplementation for different periods alters rat vascular redox parameters

Vitamin A plays physiological and antioxidants properties and is associated with protective effects on arterial level. However, deleterious effects have been reported, including those observed by our group, which has demonstrated pro-oxidant properties in other systems. Therefore, it is needed to better understand the redox effects of retinoids on arterial system. Thus, our aim was to compare vascular redox parameters among animals supplemented or not with vitamin A. Eighty-five adult male rats were treated with different retinyl palmitate doses (1,000–9,000 IU kg⁻¹ day⁻¹) or saline for 3 (25 rats, n = 5 for each group), 7 (25 rats, n = 5 for each group), and 28 (35 rats, n = 7 for each group) days periods. Aorta artery was surgically removed, cleaned to remove the blood, and homogenized. It was evaluated thiobarbituric reactive species (TBARS), total reduced sulfhydryl (SH), and activities of superoxide dismutase (SOD) and catalase (CAT). Statistics were conducted by one-way ANOVA with Dunnet’s post hoc and significance value of p ≤ 0.05. About TBARS, we observed no modifications after 3 days, but a decrease after 7 days in all doses and after 28 days in three higher doses. The two higher doses yielded an increase on SH only after 3 days. SOD activity decreased in three higher doses after 3 days and in all doses after 28 days, but no modifications after 7 days, while CAT activity increased in all doses after 3 days, decreased in all doses after 7 days, and did not change after 28 days. In conclusion, vitamin A induces antioxidant status on vascular level.     

Experimental Evidence that Phenylalanine Provokes Oxidative Stress in Hippocampus and Cerebral Cortex of Developing Rats

High levels of phenylalanine (Phe) are the biochemical hallmark of phenylketonuria (PKU), a neurometabolic disorder clinically characterized by severe mental retardation and other brain abnormalities, including cortical atrophy and microcephaly. Considering that the pathomechanisms leading to brain damage and particularly the marked cognitive impairment in this disease are poorly understood, in the present study we investigated the in vitro effect of Phe, at similar concentrations as to those found in brain of PKU patients, on important parameters of oxidative stress in the hippocampus and cerebral cortex of developing rats. We found that Phe induced in vitro lipid peroxidation (increase of TBA-RS values) and protein oxidative damage (sulfhydryl oxidation) in both cerebral structures. Furthermore, these effects were probably mediated by reactive oxygen species, since the lipid oxidative damage was totally prevented by the free radical scavengers α-tocopherol and melatonin, but not by L-NAME, a potent inhibitor of nitric oxide synthase. Accordingly, Phe did not induce nitric oxide synthesis, but significantly decreased the levels of reduced glutathione (GSH), the major brain antioxidant defense, in hippocampus and cerebral cortex supernatants. Phe also reduced the thiol groups of a commercial GSH solution in a cell-free medium. We also found that the major metabolites of Phe catabolism, phenylpyruvate, phenyllactate and phenylacetate also increased TBA-RS levels in cerebral cortex, but to a lesser degree. The data indicate that Phe elicits oxidative stress in the hippocampus, a structure mainly involved with learning/memory, and also in the cerebral cortex, which is severely damaged in PKU patients. It is therefore presumed that this pathomechanism may be involved at least in part in the severe cognitive deficit and in the characteristic cortical atrophy associated with dysmyelination and leukodystrophy observed in this disorder.     

Tenoxicam Modulates Antioxidant Redox System and Lipid Peroxidation in Rat Brain

We investigated effects of two doses of Tenoxicam, a type 2 cyclooxygenase inhibitor, administration on lipid peroxidation and antioxidant redox system in cortex of the brain in rats. Twenty-two male Wistar rats were randomly divided into three groups. First group was used as control. 10 and 20 mg/kg body weight Tenoxicam were intramuscularly administrated to rats constituting the second and third groups for 10 days, respectively. Both dose of Tenoxicam administration resulted in significant increase in the glutathione peroxidase activity, reduced glutathione and vitamins C and E of cortex of the brain. The lipid peroxidation levels in the cortex of the brain were significantly decreased by the administration. Vitamin A and β-carotene concentration was not affected by the administration. There was no statistical difference in all values between 10 and 20 mg Tenoxicam administrated groups. In conclusion, treatment of brain with 10 and 20 mg Tenoxicam has protective effects on the oxidative stress by inhibiting free radical and supporting antioxidant redox system.     

Role of Quercetin on PCBs (Aroclor-1254) Induced Impairment of Dopaminergic Receptor mRNA Expression in Cerebral Cortex of Adult Male Rats

The present study is aimed to evaluate the putative neuroprotective effect of quercetin on PCB induced impairment of dopaminergic receptor mRNA expression in cerebral cortex of adult male Wistar rats. Group I (control) received only vehicle (corn oil; 0.1 ml/kg bwt) intraperitoneally (i.p); Group II Aroclor 1254 at a dose of 2 mg/kg bwt/day (i.p); Group III (Aroclor 1254—exposed (i.p), quercetin treated gavage (50 mg/kg bwt/day); Group IV received quercetin alone (gavage). 24 h after the 30th day treatment rats were euthanized. From each rat cerebral cortex tissues was collected and analyzed for mean activities of creatine kinase, acetylcholine esterase, Na⁺/K⁺, Ca²⁺ and Mg²⁺ATPases, Hydrogen peroxide generation, protein carbonyl content and lipid peroxidation levels. The fates of the mRNA expression of dopaminergic receptors, Cacna1d on all the groups were studied by RT–PCR. Results evidenced that significant reduction of neurodegeneration in PCBs exposed rats treated with quercetin was ascertained suggesting, quercetin treatment precludes against PCB induced oxidative stress and protects dopaminergic receptor dysfunction in rat cerebral cortex.     

Effect of chromium supplementation on the diabetes induced-oxidative stress in liver and brain of adult rats

This study was designed to investigate the susceptibility of liver and brain tissues, as insulin-independent tissues, of normal adult male rats to the oxidative challenge of subchronic supplementation with chromium picolinate (CrPic) at low (human equivalent) and high doses (2.90 and 13.20 μg Cr kg⁻¹ day⁻¹, respectively). Also, the modulative effect of CrPic administration on the enhanced oxidative stress in the liver and brain tissues of alloxan-diabetic rats was studied. Fasting serum glucose level was not modified in normal rats but significantly reduced in diabetic rats that had received CrPic supplement. A mild oxidative stress was observed in the liver and brain of CrPic-supplemented normal rats confirmed by the dose-dependent reductions in the levels of hepatic and cerebral free fatty acids, superoxide dismutase and glutathione peroxidase activities, and in contrast increased tissue malondialdehyde concentration. On the other hand, hepatic and cerebral catalase activity was reduced in the high dose group only. CrPic supplementation did not act as a peroxisome proliferator confirmed by the significant reductions in liver and brain peroxisomal palmitoyl CoA oxidase activity. The non significant alterations in liver protein/DNA and RNA/DNA ratios indicate that CrPic did not affect protein synthesis per cell, and that mild elevations in hepatic total protein and RNA concentrations might be due to block or decrease in the export rate of synthesized proteins from the liver to the plasma. In diabetic rats, elevated levels of hepatic and cerebral free fatty acids and malondialdehyde, and in contrast the overwhelmed antioxidant enzymes, were significantly modulated in the low dose group and near-normalized in the high dose group. The significant increases observed in liver total protein and RNA concentrations, as well as protein/DNA and RNA/DNA ratios in diabetic rats supplemented with the high dose of Cr, compared to untreated diabetics, may be related to the improvement in the glycemic status of the diabetic animals rather than the direct effect of CrPic on protein anabolism.     

Venlafaxine Modulates Depression-Induced Oxidative Stress in Brain and Medulla of Rat

Venlafaxine is an approved antidepressant that is an inhibitor of both serotonin and norepinephrine transporters. Medical treatment with oral venlafaxine can be beneficial to depression due to reducing free radical production in the brain and medulla of depression- induced rats because oxidative stress may a play role in some depression. We investigated the effect of venlafaxine administration and experimental depression on lipid peroxidation and antioxidant levels in cortex brain, medulla and erythrocytes of rats. Thirty male wistar rats were used and were randomly divided into three groups. Venlafaxine (20 mg/kg) was orally supplemented to depression-induced rats constituting the first group for four week. Second group was depression-induced group although third group was used as control. Depressions in the first and second groups were induced on day zero of the study by chronic mild stress. Brain, medulla and erythrocytes samples were taken from all animals on day 28. Depression resulted in significant decrease in the glutathione peroxidase (GSH-Px) activity and vitamin C concentrations of cortex brain, glutathione (GSH) value of medulla although their levels were increased by venlafaxine administration to the animals of depression group. The lipid peroxidation levels in the three tissues and nitric oxide value in cortex brain elevated although their levels were decreased by venlafaxine administration. There were no significant changes in cortex brain vitamin A, erythrocytes vitamin C, GSH-Px and GSH, medulla vitamin A, GSH and GSH-Px values. In conclusion, cortex brain within the three tissues was most affected by oxidative stress although there was the beneficial effect of venlafaxine in the brain of depression-induced rats on investigated antioxidant defenses in the rat model. The treatment of depression by venlafaxine may also play a role in preventing oxidative stress. Abstract of the paper was submitted in 1st Ion Channels and Oxidative Stress Congress, 14–16 September 2006, Isparta, Turkey.     

Vitamin A (retinol) downregulates the receptor for advanced glycation endproducts (RAGE) by oxidant-dependent activation of p38 MAPK and NF-kB in human lung cancer A549 cells

As an essential component of the diet, retinol supplementation is often considered harmless and its application is poorly controlled. However, recent works demonstrated that retinol may induce a wide array of deleterious effects, especially when doses used are elevated. Controlled clinical trials have demonstrated that retinol supplementation increased the incidence of lung cancer and mortality in smokers. Experimental works in cell cultures and animal models showed that retinol may induce free radical production, oxidative stress and extensive biomolecular damage. Here, we evaluated the effect of retinol on the regulation of the receptor for advanced glycation end-products (RAGE) in the human lung cancer cell line A549. RAGE is constitutively expressed in lungs and was observed to be down-regulated in lung cancer patients. A549 cells were treated with retinol doses reported as physiologic (2 μM) or therapeutic (5, 10 or 20 μM). Retinol at 10 and 20 μM increased free radical production, oxidative damage and antioxidant enzyme activity in A549 cells. These doses also downregulated RAGE expression. Antioxidant co-treatment with Trolox®, a hydrophilic analog of α-tocopherol, reversed the effects of retinol on oxidative parameters and RAGE downregulation. The effect of retinol on RAGE was mediated by p38 MAPK activation, as blockade of p38 with PD169316 (10 μM), SB203580 (10 μM) or siRNA to either p38α (MAPK14) or p38β (MAPK11) reversed the effect of retinol on RAGE. Trolox also inhibited p38 phosphorylation, indicating that retinol induced a redox-dependent activation of this MAPK. Besides, we observed that NF-kB acted as a downstream effector of p38 in RAGE downregulation by retinol, as NF-kB inhibition by SN50 (100 μg/mL) and siRNA to p65 blocked the effect of retinol on RAGE, and p38 inhibitors reversed NF-kB activation. Taken together, our results indicate a pro-oxidant effect of retinol on A549 cells, and suggest that modulation of RAGE expression by retinol is mediated by the redox-dependent activation of p38/NF-kB signaling pathway.     

Effect of Acute Administration of 3-Butyl-1-Phenyl-2-(Phenyltelluro)Oct-En-1-One on Oxidative Stress in Cerebral Cortex,Hippocampus, and Cerebellum of Rats

Organotellurium compounds have been synthesized since 1840, but pharmacological and toxicological studies about them are still incipient. Therefore, the objective of this study was to verify the effect of acute administration of the organochalcogen 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one on some parameters of oxidative stress in the brain of 30-day-old rats. Animals were treated intraperitoneally with a single dose of the organotellurium (125, 250, or 500 μg/kg body weight) and sacrificed 60 min after the injection. The cerebral cortex, the hippocampus, and the cerebellum were dissected and homogenized in KCl. Afterward, thiobarbituric acid reactive substances (TBARS), carbonyl, sulfhydryl, catalase (CAT), superoxide dismutase (SOD), nitric oxide (NO) formation, and hydroxyl radical production were measured in the brain. The organotellurium enhanced TBARS in the cerebral cortex and the hippocampus, and increased protein damage (carbonyl) in the cerebral cortex and the cerebellum. In contrast, the compound provoked a reduced loss of thiol groups measured by the sulfhydryl assay in all the tissues studied. Furthermore, the activity of the antioxidant enzyme CAT was reduced by the organochalcogen in the cerebral cortex and the cerebellum, and the activity of SOD was inhibited in all the brain tissues. Moreover, NO production was increased in the cerebral cortex and the cerebellum by this organochalcogen, and hydroxyl radical formation was also enhanced in the cerebral cortex. Our findings indicate that this organotellurium compound induces oxidative stress in the brain of rats, corroborating that this tissue is a potential target for organochalcogen action.     

Effects of Selenium with Vitamin E and Melatonin on Cadmium-Induced Oxidative Damage in Rat Liver and Kidneys

The present study was performed to determine the protective effects of melatonin alone and vitamin E with selenium combination against cadmium-induced oxidative damage in rat liver. A total of 60 male rats were equally divided into five groups, one of which acted as control receiving subcutaneous injections of physiological saline. The remaining four groups were treated with subcutaneous injections of cadmium chloride at a dose of 1 mg/kg weight. The first study group received no treatment. The second group was treated with a combination of 60 mg/kg vitamin E and 1 mg/kg sodium selenite. Group 3 was treated with 10 mg/kg melatonin, and the four group received a combination of vitamin E, sodium selenite, and melatonin at the doses mentioned above. After 1 month, the animals were killed, and liver and kidneys were excised for histopathological inspection and determination of tissue malondialdehyde and the activity of superoxide dismutase. The animals receiving no treatment showed significantly higher malondialdehyde levels and reduced activity of superoxide dismutase (p < 0.05). Treatment with antioxidants resulted in a significant reduction in malondialdehyde when compared to nontreated animals (p < 0.05) and increase in the enzyme activity that was almost the same as the controls. The pathological findings were also in parallel with the results of the biochemical analysis. In conclusion, all the agents tested had protective effects against cadmium-induced oxidative damage.     

Administration of Histidine to Female Rats Induces Changes in Oxidative Status in Cortex and Hippocampus of the Offspring

Histidinemia is an inherited metabolic disorder biochemically characterized by high concentrations of histidine in biological fluids. Usually affected patients are asymptomatic although some individuals have mental retardation and speech disorders. Considering the high prevalence of histidinemia and the scarce information on the effects of maternal histidinemia on their progeny, we investigated various parameters of oxidative stress in brain cortex and hippocampus of the offspring from female rats that received histidine (0.5 mg/g of body weight) in the course of pregnancy and lactation. At 21 days of age we found a significant increase of thiobarbituric acid reactive substances (TBARS), 2′,7′-dihydrodichlorofluorescein oxidation, superoxide dismutase (SOD) activity, catalase (CAT) activity, total sulfhydryls and glutathione (GSH) content in cerebral cortex and hippocampus. We also verified that at 60 days of age, GSH, SOD and total sulfhydryls returned to normal levels in brain cortex, while the other parameters decreased in the same structure. In the hippocampus, at 60 days of age GSH returned to normal levels, CAT persisted elevated and the other parameters decreased. These results indicate that histidine administration to female rats can induce oxidative stress in the brain from the offspring, which partially recovers 40 days after breastfeeding stopped.     

Effects of Lead and/or Cadmium on the Oxidative Damage of Rat Kidney Cortex Mitochondria

Lead acetate (300 mg/L) and/or cadmium chloride (50 mg/L) were administered as drinking water to Sprague–Dawley rats for 8 weeks to investigate the possible combined effects of these metals on the damage in renal cortex mitochondria. Increased malonaldehyde levels due to exposure to these metals were detected by colorimetric method, which demonstrated the lipid peroxidation in the renal cortex. Ultrastructural observations and real-time quantitative PCR analyses were performed on kidney cortex pieces to identify the mitochondrial damage and quantify the relative expression levels of cytochrome oxidase subunits (COX-I/II/III), respectively. The most striking ultrastructural modifications involved distortion of mitochondrial cristae and an unusual arrangement, which were more evident when the mixture was ingested. There were significant differences in the expression levels of COX-I, II, and III between the control group and the exposed groups, whereas those in the (lead+cadmium) group were all significantly lower than that in the lead or cadmium group. In conclusion, there was an obvious synergistic oxidative damage effect of lead combined with cadmium on rat kidney cortex mitochondria, which increased defects in mitochondrial oxidative metabolism.     

L-NAME co-treatment prevent oxidative damage in the lung of adult Wistar rats treated with vitamin A supplementation

Based on the fact that vitamin A in clinical doses is a potent pro-oxidant agent to the lungs, we investigated here the role of nitric oxide (NO?) in the disturbances affecting the lung redox environment in vitamin A-treated rats (retinol palmitate, doses of 1000-9000 IU?kg(-1)?day(-1)) for 28 days. Lung mitochondrial function and redox parameters, such as lipid peroxidation, protein carbonylation and the level of 3-nytrotyrosine, were quantified. We observed, for the first time, that vitamin A supplementation increases the levels of 3-nytrotyrosine in rat lung mitochondria. To determine whether nitric oxide (NO ?) or its derivatives such as peroxynitrite (ONOO-) was involved in this damage, animals were co-treated with the nitric oxide synthase inhibitor L-NAME (30 mg?kg(-1), four times a week), and we analysed if this treatment prevented (or minimized) the biochemical disturbances resulting from vitamin A supplementation. We observed that L-NAME inhibited some effects caused by vitamin A supplementation. Nonetheless, L-NAME was not able to reverse completely the negative effects triggered by vitamin A supplementation, indicating that other factors rather than only NO? or ONOO- exert a prominent role in mediating the redox effects in the lung of rats that received vitamin A supplementation.     

Vitamin E Prevents Increase in Oxidative Damage to Lipids and DNA in Liver of ODS Rats Given Total Body X-ray Irradiation

We examined the effects of dietary vitamin E (VE) on oxidative damage to DNA and lipids in the liver a few days after total body irradiation (TBI). ODS rats, which lack vitamin C synthesis, were fed either a low VE diet (4.3 &#117 mg &#117 VE/kg) or a basal VE diet (75.6 &#117 mg &#117 VE/kg) for 5 weeks while vitamin C was supplied in the drinking water. The VE level in the liver of the low VE group was lower and the levels of lipid peroxides were higher compared to those of the basal VE group: the relative levels in the two groups were 1:30 for VE, 18:1 for 4-hydroxynonenal (HNE), and 10:1 for hexanal (HA). The level of 8-hydroxydeoxyguanosine (8OHdG), a marker of oxidative DNA damage, did not differ between the low VE and the basal VE groups. When the rats received TBI at the dose of 3 &#117 Gy and were killed on day 6, the levels of HNE, HA and 8OHdG increased by 2.2-, 2-, and 1.5-times, respectively, in the low VE group, but TBI did not cause such increases in the basal VE group. Changes in antioxidative enzymes (glutathione peroxidase, catalase, and Cu/Zn-SOD) in the liver could not explain the different responses of the two diet groups to TBI-induced oxidative damage. The concentrations of vitamin C and glutathione in the liver did not differ between the two groups. These results suggest that dietary VE can prevent the oxidative damage to DNA and lipids in the liver which appear a few days after TBI at dose of 3 &#117 Gy.