Vitamin D<Subscript>3</Subscript> Reverses the Hippocampal Cytoskeleton Imbalance But Not Memory Deficits Caused by Ovariectomy in Adult Wistar Rats

The objective of study was to investigate changes caused by ovariectomy (OVX) on aversive and non-aversive memories, as well as on cytoskeleton phosphorylating system and on vitamin D receptor (VDR) immunocontent in hippocampus. The neuroprotective role of vitamin D was also investigated. Ninety-day-old female Wistar rats were divided into four groups: SHAM, OVX, VITAMIN D and OVX + VITAMIN D; 30 days after the OVX, vitamin D supplementation (500 IU/kg), by gavage, for 30 days was started. Results showed that OVX impaired short-term and long-term recognition, and long-term aversive memories. OVX altered hippocampal cytoskeleton phosphorylating system, evidenced by the hyperphosphorylation of glial fibrillary acidic protein (GFAP), low molecular weight neurofilament subunit (NFL), medium molecular weight neurofilament subunit (NFM) and high molecular weight neurofilament subunit (NFH), and increased the immunocontent of c-Jun N-terminal protein kinases (JNK), Ca²⁺/calmodulin-dependent protein kinase II (PKCaMII) and of the sites phosphorylated lysine–serine–proline (KSP) repeats, Ser55 and Ser57. Vitamin D reversed the effects caused by OVX on cytoskeleton in hippocampus, but it was not able to reverse the effects on memory.     

Glucocorticoids may alter antioxidant enzyme capacity in the brain: baseline studies

Glucocorticoids (GCs), the adrenal steroids secreted during stress, have been shown to increase the vulnerability of hippocampal neurons to metabolic insults, potentially by altering the neuronal defense capacity against oxidative damage. These experiments assessed the effect of long term in vivo GC supplementation on basal activity of the antioxidant enzymes copper/zinc superoxide dismutase (Cu/Zn SOD), manganese superoxide dismutase (Mn SOD), catalase, and glutathione peroxidase (GSPx). Kinetic enzyme studies were done using brain tissue from the hippocampus, cortex, cerebellum, and also from liver as a peripheral control. Cu/Zn SOD activity was significantly lower in all brain regions of GC-treated rats, but higher in the liver. Mn SOD activity was unaffected by treatment. Catalase in the brain appeared largely unaffected by GC treatment, although liver catalase was significantly decreased. GSPx activity was significantly decreased by GCs at high peroxide levels in all tissues. These results indicate that the presence of GCs may lower the antioxidant capacity of tissues in a region-specific manner, and that the deficit may not appear until the tissue is challenged with supranormal levels of oxidative products (as seen with GSPx).     

Total antioxidant capacity is impaired in different structures from aged rat brain

Our data support a disproportion between free radicals levels and scavenging systems activity in different cerebral regions of the aging rat. We investigated the total reactive antioxidant potential and reactivity levels, which represent the total antioxidant capacity, in different cerebral regions of the aging rat (cortex, striatum, hippocampus and the cerebellum). In addition, we have determined several oxidative stress parameters, specifically the free radicals levels, the macromolecules damage (lipid peroxidation and carbonyl content), as well as the antioxidant enzymes activities in different cerebral areas from young (2 months-old), mature adult (6 months-old) and old (24 months-old) male Wistar rats. Free radicals levels, determined by 2′,7′-dichlorofluorescein diacetate probe, were higher in striatum, cerebellum and hippocampus from aged rats. There was an age-related increase in lipoperoxidation in hippocampus and cerebral cortex. In the cerebellum, a high activity of superoxide dismutase and a decrease of catalase activity were observed. The striatum exhibited a significant catalase activity decrease; and glutathione peroxidase activity was diminished in the hippocampus of mature and aged rats. There was a marked decrease of total antioxidant capacity in hippocampus in both reactivity and potential levels, whereas striatum and cerebral cortex displayed a reduction on reactivity assay. We suggest that age-related variations of total antioxidant defenses in brain may predispose structures to oxidative stress-related neurodegenerative disorders.     

Adenyl cyclase activator forskolin protects against Huntington’s disease-like neurodegenerative disorders

Long term suppression of succinate dehydrogenase by selective inhibitor 3-nitropropionic acid has been used in rodents to model Huntington’s disease where mitochondrial dysfunction and oxidative damages are primary pathological hallmarks for neuronal damage. Improvements in learning and memory abilities, recovery of energy levels, and reduction of excitotoxicity damage can be achieved through activation of Adenyl cyclase enzyme by a speciifc phytochemical forskolin. In this study, intraperitoneal administration of 10 mg/kg 3-nitropropionic acid for 15 days in rats notably reduced body weight, worsened motor cocordination (grip strength, beam crossing task, locomotor activity), resulted in learning and memory deifcits, greatly increased acetylcholinesterase, lactate dehydrogenase, nitrite, and malondialdehyde levels, obviously decreased adenos-ine triphosphate, succinate dehydrogenase, superoxide dismutase, catalase, and reduced glutathione levels in the striatum, cortex and hippocampus. Intragastric administration of forskolin at 10, 20, 30 mg/kg dose-de-pendently reversed these behavioral, biochemical and pathological changes caused by 3-nitropropionic acid. hTese results suggest that forskolin exhibits neuroprotective effects on 3-nitropropionic acid-induced Hun-tington’s disease-like neurodegeneration.     

Lithium and valproate modulate antioxidant enzymes and prevent ouabain-induced oxidative damage in an animal model of mania

In this study, we assessed the oxidative stress parameters in rats submitted to an animal model of mania induced by ouabain (OUA), which included the use of lithium (Li) and valproate (VPA). Li and VPA treatment reversed and prevented the OUA-induced damage in these structures, however, this effect varies depending on the brain region and treatment regimen. Moreover, the activity of the antioxidant enzymes, namely, superoxide dismutase (SOD) and catalase (CAT) was found to be increased and decreased, respectively, in the brain of OUA-administered rats. Li and VPA modulated SOD and CAT activities in OUA-subjected rats in both experimental models. Our results support the notion that Li and VPA exert antioxidant-like properties in the brain of rats submitted to animal model of mania induced by ouabain.     

Oxidative stress in the hippocampus, anxiety-like behavior and decreased locomotory and exploratory activity of adult rats: effects of sub acute vitamin A supplementation at therapeutic doses

Vitamin A participates in the maintenance of normal hippocampal function during embryonic and postnatal stages of the vertebrate life. Some works demonstrated that vitamin A metabolites impair learning and induce a depression-like behavior in mice, among other effects. Since vitamin A has prooxidant effects on other experimental models, we decided to investigate whether vitamin A can induce oxidative stress in the adult rat hippocampus. We analyzed the sub acute effects of therapeutic (1000 and 2500 I.U./kg) or excessive (4500 and 9000 I.U./kg) vitamin A doses on the hippocampal redox state, as well as on levels of anxiety, and locomotory and exploratory activity. Vitamin A supplementation induced lipid peroxidation, protein carbonylation, and oxidation of the protein thiol content in the rat hippocampus in all periods analyzed. Increased superoxide dismutase (SOD) activity and decreased catalase (CAT) activity were also observed, which gives rise to an imbalance in the principal cellular enzymatic antioxidant system. Then, our results show, for the first time, that vitamin A induced oxidative stress in the adult rat hippocampus, is anxiogenic, and decreases locomotion in and exploration of an open field.     

Calcium and zinc supplementation protects lead (Pb)-induced perturbations in antioxidant enzymes and lipid peroxidation in developing mouse brain

Several studies have implicated oxidative stress as one of the important mechanisms of toxic effects of lead (Pb). In the present study we tested the beneficial effects of calcium (Ca²⁺) and zinc (Zn²⁺) in protecting the Pb-induced oxidative stress in the brains of developing and adult mice. Mice were lactationally exposed to 0.2% Pb and supplemented with either calcium (Ca²⁺) or zinc (Zn²⁺) and the mitochondrial antioxidant enzymes [superoxide dismutase (SOD), xanthine oxidase (XO) and catalase (CAT)] and lipid peroxidation (LP) were analyzed in cortex, hippocampus, cerebellum and medulla of brains excised on postnatal day (PND) 14, 21, 28 and 3 months. The levels of free radicals were measured using direct Electron Paramagnetic Resonance (EPR) spectroscopy. Exposure to Pb resulted a significant decrease in the activities of SOD, XO and CAT while the LP levels were significantly increased in different brain regions. Evaluation of EPR signals and g-values showed abundant accumulation of free radicals in different regions of the brain following Pb exposure. Interestingly the supplementation with Ca²⁺ or Zn²⁺ reversed the Pb-induced effects on antioxidant enzymes, LP and free radical formation; however Zn²⁺ supplementation appeared to be more protective. These findings strongly support that zinc and calcium supplementation significantly protect the Pb-induced oxidative stress, a major contributing factor to neurotoxicity.     

Age-dependent modulation of hippocampal long-term potentiation by antioxidant enzymes

Oxidative stress has long been associated with normal aging and age-related neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). However, it is now evident that reactive oxygen species (ROS) such as superoxide (O(2-*)) and hydrogen peroxide (H(2)O(2)) also play pivotal roles in normal cell signaling. The focus of the present study was to examine the effects of the antioxidant enzymes CuZnSOD (SOD1) and catalase, which produce and remove H(2)O(2), respectively, on long-term potentiation (LTP) forms of synaptic plasticity during aging. Consistent wth previous studies, LTP, when induced in vitro in CA1 of the hippocampus with a high-frequency stimulation protocol, is significantly reduced in slices from older mice (22-26 months) relative to younger mice (2-4 months). Neither knockout of the endogenous catalase gene (Cat KO) nor acute enzymatic treatment with SOD1 altered LTP in slices from adult mice. Conversely, enzymatic applications of SOD1 inhibited LTP in slices from older mice. A much different set of results emerges with exogenous applications of catalase to hippocampal slices. Catalase significantly inhibited LTP in slices from adult mice but reversed age-related LTP deficits in slices from older mice. Measurements of H(2)O(2) showed that exogenous treatments with catalase lowered H(2)O(2) in synapse-enriched synaptoneurosome (SN) fractions prepared from adult mice. Notably, SNs from both Cat KO and old mice were deficient in removing extracellular challenges of H(2)O(2). Overall, the results suggest that dynamic alterations in extracellular H(2)O(2) metabolism affect synaptic plasticity in the hippocampus during aging.     

Chronic Mild Hyperhomocysteinemia Alters Inflammatory and Oxidative/Nitrative Status and Causes Protein/DNA Damage,as well as Ultrastructural Changes in Cerebral Cortex: Is Acetylsalicylic Acid Neuroprotective?

Homocysteine is a sulfur-containing amino acid derived from methionine metabolism. When plasma homocysteine levels exceed 10–15 μM, there is a condition known as hyperhomocysteinemia, which occur as a result of an inborn error of methionine metabolism or by non-genetic causes. Mild hyperhomocysteinemia is considered a risk factor for development of neurodegenerative diseases. The objective of the present study was to evaluate whether acetylsalicylic acid has neuroprotective role on the effect of homocysteine on inflammatory, oxidative/nitrative stress, and morphological parameters in cerebral cortex of rats subjected to chronic mild hyperhomocysteinemia. Wistar male rats received homocysteine (0.03 μmol/g of body weight) by subcutaneous injections twice a day and acetylsalicylic acid (25 mg/Kg of body weight) by intraperitoneal injections once a day from the 30th to the 60th postpartum day. Control rats received vehicle solution in the same volume. Results showed that rats subjected to chronic mild hyperhomocysteinemia significantly increased IL-1β, IL-6, and acetylcholinesterase activity and reduced nitrite levels. Homocysteine decreased catalase activity and immunocontent and superoxide dismutase activity, caused protein and DNA damage, and altered neurons ultrastructure. Acetylsalicylic acid totally prevented the effect of homocysteine on acetylcholinesterase activity and catalase activity and immunocontent, as well as the ultrastructural changes, and partially prevented alterations on IL-1β levels, superoxide dismutase activity, sulfhydryl content, and comet assay. Acetylsalicylic acid per se increased DNA damage index. In summary, our findings showed that chronic chemically induced model of mild hyperhomocysteinemia altered some parameters and acetylsalicylic acid administration seemed to be neuroprotective, at least in part, on neurotoxicity of homocysteine.     

Effects of mood stabilizers on DNA damage in an animal model of mania

Objective

Recent studies have suggested that oxidative stress and DNA damage may play a role in the pathophysiology of bipolar disorder (BD). We investigated the effects of the mood stabilizers lithium and valproate on amphetamine-induced DNA damage in an animal model of mania and their correlation with oxidative stress markers.

Methods

In the first experiment (reversal model), we treated adult male Wistar rats with D-amphetamine (AMPH) or saline for 14 days; between the 8th and 14th days, rats also received lithium, valproate or saline. In the second experiment (prevention model), rats received either lithium, valproate or saline for 14 days; between the 8th and 14th days, we added AMPH or saline. We evaluated DNA damage using single-cell gel electrophoresis (comet assay), and we assessed the mutagenic potential using the micronucleus test. We assessed oxidative stress levels by lipid peroxidation levels (TBARS) and antioxidant enzyme activities (superoxide dismutase and catalase). We assessed DNA damage and oxidative stress markers in blood/plasma and hippocampal samples. We evaluated mutagenesis in fresh lymphocytes.

Results

In both models, we found that AMPH increased peripheral and hippocampal DNA damage. The index of DNA damage correlated positively with lipid peroxidation, whereas lithium and valproate were able to modulate the oxidative balance and prevent recent damage to the DNA. However, lithium and valproate were not able to prevent micronucleus formation.

Conclusion

Our results support the notion that lithium and valproate exert central and peripheral antioxidant-like properties. In addition, the protection to the integrity of DNA conferred by lithium seems to be limited to transient DNA damage and does not alter micronuclei formation.Medical subject headings: models, animal; bipolar disorder; lithium; DNA damage; dopamine; oxidative stress     

Free radical scavenging systems in developing rat brain

Because the developing brain is subject to high oxygen tension and lacks a functional bloodbrain anti-oxidant protection is important to development in the brain. The levels of superoxide dismutase, copper-zinc superoxide dismutase, manganese superoxide dismutase, catalase, glutathione and related enzymes, namely, glutathione reductase and glutathione peroxidase were determined in rat brain at various stages of development. The levels of thiobarbituric acid reactive products, indicative of lipid peroxidation, were very low at birth and increased to adult levels by the 16th day after birth. Brain glutathione levels displayed significant variations during the first 2 weeks after birth but not thereafter. Catalase activity in developing brain slowly increased over 45 days. Total superoxide dismutase activity in 1-day-old rat brain, 80% of the adult rat brain level, subsequently decreased on day 6. Total superoxide dismutase activity, however, increased again in 10-day-old rats and remained constant thereafter. While the developmental pattern of manganese superoxide dismutase was similar to that of the total superoxide dismutase, the copper-zinc superoxide dismutase levels were low at birth and reached adult levels on the 10th day after birth. There was no variation in glutathione reductase and peroxidase levels except for a decrease on day 16 of glutathione reductase and slow increase in adult levels by day 28. The present findings suggest that the overall levels of antioxidant enzymes in the developing brain are comparable to a large extent to those present in the adult brain. In contrast to the developing brain, hepatic levels of glutathione, total superoxide dismutase, manganese superoxide dismutase are significantly lower at birth and increase during development.     

Suppression of experimental autoimmune neuritis by the oxygen radical scavengers superoxide dismutase and catalase

Macrophages have been implicated in myelin damage in experimental autoimmune neuritis (EAN). We examined a possible pathogenetic role of toxic oxygen species elaborated by macrophages in EAN by administering oxygen radical scavengers. Early treatment of rats with either catalase or superoxide dismutase (10,000 U/kg/day) protected animals from the development of EAN. Treatment delayed until there was clinical manifestation of EAN (day 13) still markedly attenuated the severity of the disease, as evidenced by clinical assessment, electrophysiological studies, and morphological observation. In cell culture, macrophages from sham-treated controls generated heightened oxidative metabolic responses indicating in vivo macrophage activation. Addition of catalase or superoxide dismutase abrogated or diminished chemiluminescence and production of reactive oxygen intermediates by macrophages ex vivo. Our findings underscore the importance of macrophages in EAN and provide evidence that, in this model, macrophagederived reactive oxygen intermediates contribute to damage of the myelin sheath.     

Effects of basic fibroblast growth factor on superoxide dismutase activity and malondialdehyde content in the rat brain following intracerebral hemorrhage

BACKGROUND: Studies have confirmed that basic fibroblast growth factor (bFGF) promotes neuronal survival and neurite outgrowth. OBJECTIVE: To compare and verify the effects of bFGF on superoxide dismutase activity and malondialdehyde content in rat brain tissues surrounding a hemorrhagic lesion, as well as the hippocampus at the hemorrhagic side. DESIGN, TIME AND SETTING: The randomized, controlled, neurobiological study was performed at the Science Experimental Center and Research Laboratory, Guangxi Medical University, China, from September to December 2006. MATERIALS: Ninety-two adult, healthy, Wistar rats of equal gender were used to establish intraeerebral hemorrhage by infusing type VII collagenase into the left internal capsule. Type Ⅶ collagenase (Sigma, USA), superoxide dismutase and malondialdehyde kits (Jiancheng, China), and bFGF (Institute of Bioengineering, Ji'nan University, China) were used for this study. METHODS: Ninety successfully lesioned rats were equally and randomly divided into three groups. Rats in the bFGF group were intramuscularly injected daily with bFGF (8μg/kg). Rats in the saline control group received an equal volume of saline. The rats in the model group did not receive other interventions. Superoxide dismutase activity was measured using the xanthine oxidase method. Malondialdehyde contents were detected using the thiobarbituric acid method. MAIN OUTCOME MEASURES: At 1, 3, and 7 days following intracerebral hemorrhage, superoxide dismutase and malondialdehyde were determined in the brain tissue surrounding the hematoma and in the hippocampus in the affected hemisphere. RESULTS: In brain tissue surrounding the hematoma, superoxide dismutase activity was significantly increased in the bFGF group at 3 and 7 days after intracerebral hemorrhage compared with the saline control group, whereas malondialdehyde content was significantly decreased (P < 0.05). In the hippocampus, superoxide dismutase activity was significantly increased in the bFGF group at 7 days following intracerebral hemorrhage compared with the saline control group, whereas malondialdehyde content was significantly decreased (P < 0.05). At 1, 3, and 7 days after intracerebral hemorrhage, there was no significant difference between the saline control group and the model group with regards to parameter or brain region (P > 0.05). CONCLUSION: Increased superoxide dismutase activity and decreased malondialdehyde content were detected in tissue surrounding the hematoma, as well as the ipsilateral hippocampus, of intracerebral hemorrhage rats treated with bFGF. Changes in these parameters were detected earlier in tissue adjacent to the lesion, compared with the ipsilateral hippocampus.     

Tanshinone I alleviates motor and cognitive impairments via suppressing oxidative stress in the neonatal rats after hypoxic-ischemic brain damage

Neonatal hypoxia-ischemia is one of the main reasons that cause neuronal damage and neonatal death. Several studies have shown that tanshinone I (TsI), one of the major ingredients of Danshen, exerts potential neuroprotective effect in adult mice exposed to permanent left cerebral ischemia. However, it is unclear whether administration of TsI has neuroprotective effect on neonatal hypoxic-ischemic brain damage (HIBD), and if so, the potential mechanisms also remain unclear. Here, we reported that treatment with TsI (5 mg/kg, i.p.) significantly alleviated the deficits of myodynamia and motor functions as well as the spatial learning and memory in the rat model of HIBD. These behavioral changes were accompanied by a significant decrease in the number of neuronal loss in the CA1 area of hippocampus. Moreover, ELISA assay showed that TsI significantly increased the production of antioxidants including total antioxidant capacity (T-AOC), glutathione (GSH), total superoxide dismutase (T-SOD) and catalase (CAT), and reduced the production of pro-oxidants including hydrogen peroxide (H₂O₂), total nitric oxide synthase (T-NOS) and inducible nitric oxide synthase (iNOS). Taken together, these results indicate that TsI presents potential neuroprotection against neuronal damage via exerting significantly antioxidative activity and against pro-oxidant challenge, thereby ameliorating hypoxia-ischemia-induced motor and cognitive impairments in the neonatal rats, suggesting that TsI may be a potential therapeutic agent against HIBD.     

Effects of lithium and valproate on amphetamine-induced oxidative stress generation in an animal model of mania

OBJECTIVE: Previous studies have suggested that oxidative stress may play a role in the pathophysiology of bipolar disorder (BD). Moreover, recent studies indicate that lithium and valproate exert neuroprotective effects against oxidative stress. We studied the effects of the mood stabilizers lithium and valproate on amphetamine-induced oxidative stress in an animal model of mania. METHODS: In the first model (reversal treatment), adult male Wistar rats received d-amphetamine or saline for 14 days, and between the 8th and 14th days, they were treated with lithium, valproate or saline. In the second model (prevention treatment), rats were pretreated with lithium, valproate or saline, and between the 8th and 14th days, they received d-amphetamine or saline. We assessed locomotor activity with the open-field task. We measured thiobarbituric acid reactive substances (TBARS) and protein carbonyl formation, as parameters of oxidative stress, and superoxide dismutase (SOD) and catalase (CAT), the major antioxidant enzymes, in the prefrontal cortex and hippocampus. RESULTS: Lithium and valproate reversed (reversal treatment model) and prevented (prevention treatment model) amphetamine-induced hyperactivity and reversed and prevented amphetamine-induced TBARS formation in both experiments. However, the co-administration of lithium or valproate with amphetamine increased lipid peroxidation, depending on the brain region and treatment regimen. No changes in protein carbonyl formation were observed. SOD activity varied with different treatment regimens, and CAT activity increased when the index of lipid peroxidation was more robust. CONCLUSION: Our findings suggest that lithium and valproate exert protective effects against amphetamine-induced oxidative stress in vivo, further supporting the hypothesis that oxidative stress may be associated with the pathophysiology of BD.     

Physical exercise reverses glutamate uptake and oxidative stress effects of chronic homocysteine administration in the rat

The influence of physical exercise on the effects elicited by homocysteine on glutamate uptake and some parameters of oxidative stress, namely thiobarbituric acid-reactive substances, 2',7'-dichlorofluorescein (H(2)DCF) oxidation, as well as enzymatic antioxidant activities, superoxide dismutase, catalase and glutathione peroxidase in rat cerebral cortex were investigated. Wistar rats received subcutaneous administration of homocysteine or saline (control) from the 6th to 29th day of life. The physical exercise was performed from the 30th to 60th day of life; 12 h after the last exercise session animals were sacrificed and the cerebral cortex was dissected out. It is shown that homocysteine reduces glutamate uptake increases thiobarbituric acid-reactive substances and disrupts enzymatic antioxidant defenses in cerebral cortex. Physical activity reversed the homocysteine effects on glutamate uptake and on antioxidant enzymes activities; although the increase in thiobarbituric acid-reactive substances was only partially reversed by exercise. These findings allow us to suggest that physical exercise may have a protective role against homocysteine-induced oxidative imbalance and brain damage to the glutamatergic system.     

Estradiol--induced redistribution of glial fibrillary acidic protein immunoreactivity in the rat brain

The immunohistochemical distribution of the glial fibrillary acidic protein (GFAP), a marker of glial filaments, was studied on coronal sections of the globus pallidus, the area CA4 of the hippocampus and the arcuate nucleus of the hypothalamus, 3 estrogen-sensitive areas of the rat brain. The number and the surface density of the GFAP-immunoreactive cells were evaluated in 6 adult ovariectomized rats injected with a single dose (20 mg/kg) of estradiol valerate (OVX + E2 rats) and in 6 ovariectomized littermates injected with vehicle (OVX rats). Two days after the injection, a similar distribution of the GFAP was observed in the arcuate nucleus of OVX + E2 rats when compared to OVX rats, whereas a significantly (P less than 0.001) increased surface density of GFAP immunoreactive material was observed in the globus pallidus and hippocampus of estradiol-treated rats. Since the number of GFAP-positive cells was unchanged by the estradiol injection, the enhanced surface density of GFAP immunoreactive material in the hippocampus and globus pallidus suggest a possible influence of estradiol on GFAP-immunoreactive glial processes.     

DNA damage in rats after treatment with methylphenidate

BACKGROUND: Methylphenidate (MPH) is a widely prescribed psychostimulant for the treatment of attention-deficit hyperactivity disorder (ADHD). Recently, some studies have addressed the genotoxic potential of the MPH, but the results have been contradictory. Hence, the present study aimed to investigate the index of cerebral and peripheral DNA damage in young and adult rats after acute and chronic MPH exposure. METHODS: We used (1) single cell gel electrophoresis (Comet assay) to measure early DNA damage in hippocampus, striatum and total blood, and (2) micronucleus test in total blood samples. RESULTS: Our results showed that MPH increased the peripheral index of early DNA damage in young and adult rats, which was more pronounced with chronic treatment and in the striatum compared to the hippocampus. Neither acute nor chronic MPH treatment increased micronucleus frequency in young or in adult rats. Peripheral DNA damage was positively correlated with striatal DNA damage. CONCLUSION: These results suggest that MPH may induce central and peripheral early DNA damage, but this early damage may be repaired.     

Attenuation of senescence-induced oxidative exacerbations in aged rat brain by (−)-epigallocatechin-3-gallate

Aging is a complex biological phenomenon which involves free radicals and oxidative stress. Brain is more susceptible and vulnerable to oxidative damage due to its high-polyunsaturated fatty acid content and high rate of aerobic metabolism. Since the antioxidant defense system is diminished during aging, antioxidant supplementation might be a protective strategy against age-associated oxidative damage. The present study evaluates the antioxidant potential of (-)-epigallocatechin-3-gallate (EGCG), a major polyphenol present in green tea against age-associated oxidative damage in rat brain. Male albino rats of Wistar strain were used in the study. Group I (young) and Group II (aged) rats received saline alone orally for 30 days. Group III (young) and Group IV (aged) rats received EGCG (2mg/kg body weight/day) orally for 30 days. Antioxidant status and oxidative damage were assessed. EGCG brought about an augmentation in the activities of enzymic antioxidants like superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and improved the non-enzymic antioxidants like tocopherol, ascorbic acid and glutathione. EGCG ameliorated the malondialdehyde and protein carbonyl levels. Thus, EGCG has emerged out as a good antioxidant neutraceutical and a neuroprotective agent in alleviating the age-associated oxidative damage in aged rat brain.     

The activities of key antioxidant enzymes in the early postnatal development of rats

In this study, we investigated the activities of several antioxidant enzymes during the postnatal development of the brain and liver of rats. Experiments were performed on male rats of different ages, viz., 5, 10, 20, 30, and 90 days, so that the different periods of the brain development could be investigated. The activity of the enzymes of the antioxidant system (superoxide dismutase, catalase, and glutathione peroxidase) in the immature brain was found to be lower than in the brains of adult animals. Cytoplasmic superoxide dismutase was an exception: its activity declined along with development in both brain and liver. High activity of antioxidant enzymes on day 5 of postnatal development in rats was found, which may be associated with the adaptation to the environment with increased oxygen content. Our results led to the conclusion that the formation of the antioxidant system in the postnatal development of the brain is accompanied by redistribution of the enzyme activity between subcellular fractions, as well as changes in the contributions of the main pathways of Н₂О₂ elimination: the activity of glutathione system enzymes increases and the catalase activity decreases.