共查询到20条相似文献,搜索用时 31 毫秒
1.
Livia G. R. P. Macêdo Milena Carvalho-Silva Gabriela K. Ferreira Júlia S. Vieira Natália Olegário Renata C. Gonçalves Francieli S. Vuolo Gustavo C. Ferreira Patrícia F. Schuck Felipe Dal-Pizzol Emilio L. Streck 《Neurochemical research》2013,38(12):2625-2630
Tyrosinemia type II, also known as Richner–Hanhart syndrome, is an autosomal recessive inborn error of metabolism caused by a deficiency of hepatic cytosolic tyrosine aminotransferase, and is associated with neurologic and development difficulties in numerous patients. Considering that the mechanisms underlying the neurological dysfunction in hypertyrosinemic patients are poorly known and that studies demonstrated that high concentrations of tyrosine provoke oxidative stress in vitro and in vivo in the cerebral cortex of rats, in the present study we investigate the oxidative stress parameters (enzymatic antioxidant defenses, thiobarbituric acid-reactive substances and protein carbonyl content) in cerebellum, hippocampus and striatum of 30-old-day rats after acute administration of l-tyrosine. Our results demonstrated that the acute administration of l-tyrosine increased the thiobarbituric acid reactive species levels in hippocampus and the carbonyl levels in cerebellum, hippocampus and striatum. In addition, acute administration of l-tyrosine significantly decreased superoxide dismutase activity in cerebellum, hippocampus and striatum, while catalase was increased in striatum. In conclusion, the oxidative stress may contribute, along with other mechanisms, to the neurological dysfunction characteristic of hypertyrosinemia and the administration of antioxidants may be considered as a potential adjuvant therapy for tyrosinemia, especially type II. 相似文献
2.
Emilio L. Streck Samira D. T. De Prá Paula Ronsani Ferro Milena Carvalho-Silva Lara M. Gomes Jotele F. Agostini Adriani Damiani Vanessa M. Andrade Patrícia F. Schuck Gustavo C. Ferreira Giselli Scaini 《Molecular and cellular biochemistry》2017,435(1-2):207-214
Tyrosine levels are abnormally elevated in tissues and body fluids of patients with inborn errors of tyrosine metabolism. Tyrosinemia type II, which is caused by tyrosine aminotransferase deficiency, provokes eyes, skin, and central nervous system disturbances in affected patients. However, the mechanisms of brain damage are still poorly known. Considering that studies have demonstrated that oxidative stress may contribute, along with other mechanisms, to the neurological dysfunction characteristic of hypertyrosinemia, in the present study we investigated the effects of antioxidant treatment (NAC and DFX) on DNA damage and oxidative stress markers induced by chronic administration of l-tyrosine in cerebral cortex, hippocampus, and striatum of rats. The results showed elevated levels of DNA migration, and thus DNA damage, after chronic administration of l-tyrosine in all the analyzed brain areas, and that the antioxidant treatment was able to prevent DNA damage in cerebral cortex and hippocampus. However, the co-administration of NAC plus DFX did not prevent the DNA damage in the striatum. Moreover, we found a significant increase in thiobarbituric acid-reactive substances (TBA-RS) and DCFH oxidation in cerebral cortex, as well as an increase in nitrate/nitrite levels in the hippocampus and striatum. Additionally, the antioxidant treatment was able to prevent the increase in TBA-RS levels and in nitrate/nitrite levels, but not the DCFH oxidation. In conclusion, our findings suggest that reactive oxygen and nitrogen species and oxidative stress can play a role in DNA damage in this disorder. Moreover, NAC/DFX supplementation to tyrosinemia type II patients may represent a new therapeutic approach and a possible adjuvant to the current treatment of this disease. 相似文献
3.
Carolina Didonet Pederzolli Andrea Pereira Rosa Amanda Szekir de Oliveira Juliana G. Coelho Débora da Luz Becker Giovana Reche Dalazen Tarsila Barros Moraes Carlos S. Dutra-Filho 《Molecular and cellular biochemistry》2010,344(1-2):231-239
N-Acetylaspartic acid (NAA) accumulates in Canavan disease, a severe inherited neurometabolic disorder clinically characterized by mental retardation, hypotonia, macrocephaly, and seizures. The mechanisms of brain damage in this disease remain poorly understood. Recent studies developed by our research group showed that NAA induces oxidative stress in vitro and in vivo in cerebral cortex of rats. Lipoic acid is considered as an efficient antioxidant which can easily cross the blood–brain barrier. Considering the absence of specific treatment to Canavan disease, this study evaluates the possible prevention of the oxidative stress promoted by NAA in vivo by the antioxidant lipoic acid to preliminarily evaluate lipoic acid efficacy against pro-oxidative effects of NAA. Fourteen-day-old Wistar rats received an acute administration of 0.6 mmol NAA/g body weight with or without lipoic acid (40 mg/kg body weight). Catalase (CAT), glutathione peroxidase (GPx), and glucose 6-phosphate dehydrogenase activities, hydrogen peroxide content, thiobarbituric acid-reactive substances (TBA-RS), spontaneous chemiluminescence, protein carbonyl content, total antioxidant potential, and DNA–protein cross-links were assayed in the cerebral cortex of rats. CAT, GPx activities, and total antioxidant potential were significantly reduced, while hydrogen peroxide content, TBA-RS, spontaneous chemiluminescence, and protein carbonyl content were significantly enhanced by acute administration of NAA. Those effects were all prevented by lipoic acid pretreatment. Our results clearly show that lipoic acid may protect against the oxidative stress promoted by NAA. This could represent a new therapeutic approach to the patients affected by Canavan disease. 相似文献
4.
Sgaravatti AM Sgarbi MB Testa CG Durigon K Pederzolli CD Prestes CC Wyse AT Wannmacher CM Wajner M Dutra-Filho CS 《Neurochemistry international》2007,50(3):564-570
GHB is a naturally occurring compound in the central nervous system (CNS) whose tissue concentration are highly increased during drug abuse and in the inherited deficiency of succinic semialdehyde dehydrogenase (SSADH) activity. SSADH deficiency is a neurometabolic-inherited disorder of the degradation pathway of gamma-aminobutyric acid (GABA). It is biochemically characterized by increased concentrations of gamma-hydroxybutyric acid (GHB) in tissues, cerebrospinal fluid (CSF), blood and urine of affected patients. Clinical manifestations are variable, ranging from mild retardation of mental, motor, and language development to more severe neurological symptoms, such as hypotonia, ataxia and seizures, whose underlying mechanisms are practically unknown. In the present study, the in vitro and in vivo effects of GHB was investigated on some parameters of oxidative stress, such as chemiluminescence, thiobarbituric acid-reactive substances (TBA-RS), total radical-trapping antioxidant potential (TRAP), total antioxidant reactivity (TAR), as well as the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in homogenates from cerebral cortex of 15-day-old Wistar rats. In vitro, GHB significantly increased chemiluminescence and TBA-RS levels, while TRAP and TAR measurements were markedly diminished. In contrast, the activities of the antioxidant enzymes SOD, CAT and GPX were not altered by GHB in vitro. Acute administration of GHB provoked a significant enhance of TBA-RS levels and a decrease of TRAP and TAR measurements. These results indicate that GHB induces oxidative stress by stimulating lipid peroxidation and decreasing the non-enzymatic antioxidant defenses in cerebral cortex of young rats. If these effects also occur in humans, it is possible that they might contribute to the brain damage found in SSADH-deficient patients and possibly in individuals who consume GHB or its prodrug gamma-butyrolactone. 相似文献
5.
Karowicz-Bilinska A Plodzidym M Krol J Lewinska A Bartosz G 《Redox report : communications in free radical research》2008,13(5):237-240
The levels of urinary hydrogen peroxide and thiobarbituric acid reactive substances have been compared during the menstrual cycle of 12 regularly menstruating women. Higher level of both indices of oxidative stress (normalized with respect to creatinine content) were found in the luteal phase of the cycle. These results give further evidence for the usefulness of urinary hydrogen peroxide and thiobarbituric acid reactive substances as potential biomarkers of oxidative stress and for the antioxidant action of estrogens. 相似文献
6.
Medeiros MC Mello A Gemelli T Teixeira C de Almeida M de Andrade RB Wannmacher CM Guerra RB Gomez R Funchal C 《Neurochemical research》2012,37(5):928-934
Selenium (Se) is an essential mineral for mammals. It is a nutrient related to the complex metabolic and enzymatic functions.
Although Se has important physiological functions in the cells, organic compounds of Se can be extremely toxic, and may affect
the central nervous system. This study aims to investigate the effect of the chronic treatment with the vinyl chalcogenide
3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on some parameters of oxidative stress in the brain of rats. Animals received
the vinyl chalcogenide (125, 250 or 500 μg/kg body weight) intraperitoneally once a day during 30 days. 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) and glutathione peroxidase (GPx) activities were
measured in the brain. Results showed that the organoselenium enhanced TBARS in the cerebral cortex of rats but the compound
was not able to change carbonyl levels. Furthermore, the organoselenium reduced thiol groups measured by the sulfhydryl assay
in all tissues studied. The activity of the antioxidant enzyme CAT was increased by the organochalcogen in the cerebral cortex
and in the cerebellum, and the activity of SOD was increased in the hippocampus. On the other hand, the activity of the antioxidant
enzyme GPx was reduced in all brain structures. Our findings indicate that this organoselenium compound induces oxidative
stress in different brain regions of rats, corroborating to the fact that this tissue is a potential target for organochalcogen
action. 相似文献
7.
Cláudia Funchal Carlos Augusto Souza Carvalho Tanise Gemelli Andressa S. Centeno Robson Brum Guerra Mirian Salvador Caroline Dani Adriana Coitinho Rosane Gomez 《Cellular and molecular neurobiology》2010,30(7):1135-1142
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. 相似文献
8.
Agostinho FR Jornada LK Schröder N Roesler R Dal-Pizzol F Quevedo J 《Neurochemical research》2007,32(8):1343-1350
Decreased antioxidant activity is considered as one of the causes of tardive dyskinesia in schizophrenic patients in a prolonged
neuroleptic treatment course. Haloperidol (HAL) has been hypothesized to increase oxidative stress, while clozapine (CLO)
would produce less oxidative damage. The objective was to determine whether CLO for 28 days could reverse or attenuate HAL-induced
oxidative damage in animals previously treated with HAL for 28 days. HAL significantly increased thiobarbituric acid reactive
substances levels in the cortex (CX) and striatum and increased protein carbonyls in hippocampus (HP) and CX and this was
not attenuated by CLO treatment. In the total radical trapping antioxidant parameter assay there was a decrease in the HP
total antioxidant potential induced by HAL and by treatment with HAL + CLO. Our findings demonstrated that the atypical antipsychotic
CLO could not revert oxidative damage caused by HAL. 相似文献
9.
Kaizer RR Corrêa MC Spanevello RM Morsch VM Mazzanti CM Gonçalves JF Schetinger MR 《Journal of inorganic biochemistry》2005,99(9):1865-1870
Aluminum (Al), oxidative stress and impaired cholinergic functions have all been related to Alzheimer's disease (AD). The present study evaluates the effect of aluminum on acetylcholinesterase (AChE) and lipid peroxidation in the mouse brain. Mice were loaded by gavage with Al 0.1 mmol/kg/day 5 days per week during 12 weeks. The mice were divided into four groups: (1) control; (2) 10 mg/mL of citrate solution; (3) 0.1 mmol/kg of Al solution; (4) 0.1 mmol/kg of Al plus 10 mg/mL of citrate solution. AChE activity was determined in the hippocampus, striatum, cortex, hypothalamus and cerebellum and lipid peroxidation was determined in the hippocampus, striatum and cortex. An increase of AChE activity was observed in the fourth group (Al + Ci) in the hippocampus (36%), striatum (54%), cortex (44%) and hypothalamus (22%) (p<0.01). The third group (Al) presented a decrease of AChE activity in the hypothalamus (20%) and an enhancement in the striatum (27%). Lipid peroxidation, measured by TBARS (thiobarbituric acid reactive substances), was elevated in the hippocampus and cerebral cortex when compared with the control (p < 0.01). The effect of aluminum on AChE activity may be due to a direct neurotoxic effect of the metal or perhaps a disarrangement of the plasmatic membrane caused by increased lipid peroxidation. 相似文献
10.
Patrícia F. Schuck Paula C. Ceolato Gustavo C. Ferreira Anelise Tonin Guilhian Leipnitz Carlos S. Dutra-Filho 《Free radical research》2013,47(11):1261-1272
Patients affected by medium-chain acyl-CoA dehydrogenase deficiency (MCADD) suffer from acute episodes of encephalopathy whose underlying mechanisms are poorly known. The present work investigated the in vitro effect of cis-4-decenoic acid (cDA), which accumulates in MCADD, on important parameters of oxidative stress in cerebral cortex of young rats. cDA markedly induced lipid peroxidation, as verified by the increased levels of spontaneous chemiluminescence and thiobarbituric acid-reactive substances. Furthermore, cDA significantly increased carbonyl formation and sulphydryl oxidation, which is indicative of protein oxidative damage, and promoted 2′,7′-dihydrodichlorofluorescein oxidation. It was also observed that the non-enzymatic tissue antioxidant defenses were decreased by cDA, whereas the antioxidant enzyme activities catalase, superoxide dismutase and glutathione peroxidase were not altered. Moreover, cDA-induced lipid peroxidation and GSH reduction was totally blocked by free radical scavengers, suggesting that reactive species were involved in these effects. The data indicate that oxidative stress is induced by cDA in rat brain in vitro and that oxidative damage might be involved in the pathophysiology of the encephalopathy in MCADD. 相似文献
11.
《Free radical biology & medicine》1999,26(3-4):371-378
Metabolic abnormalities observed in retina and in cerebral cortex were compared in diabetic rats and experimentally galactosemic rats. Diabetes or experimental galactosemia of 2 months duration significantly increased oxidative stress in retina, as shown by elevation of retinal thiobarbituric acid reactive substances (TBARS) and subnormal activities of antioxidant defense enzymes, but had no such effect in the cerebral cortex. Activities of sodium potassium adenosine triphosphatase [(Na,K)-ATPase] and calcium ATPase became subnormal in retina as well as in cerebral cortex. In contrast, protein kinase C (PKC) activity was elevated in retina but not in cerebral cortex in the same hyperglycemic rats. Dietary supplementation with an antioxidant mixture (containing ascorbic acid, Trolox, α-tocopherol acetate, N-acetyl cysteine, β-carotene, and selenium) prevented the diabetes- induced and galactosemia-induced elevation of retinal oxidative stress, the elevation of retinal PKC activity and the decrease of retinal ATPases. In cerebral cortex, administration of the antioxidant diet also prevented the diabetes-induced decreases in (Na,K)-ATPase and calcium ATPases, but had no effect on TBARS and activities of PKC and antioxidant-defense enzymes. The results indicate that retina and cerebral cortex differ distinctly in their response to elevation of tissue hexose, and that cerebral cortex is more resistant than retina to diabetes-induced oxidative stress. The greater resistance to oxidative stress in cerebral cortex, as compared to retina, is consistent with the resistance of cerebral cortex to microvascular disease in diabetes, and with a hypothesis that oxidative stress contributes to microvascular disease in diabetes. Dietary supplementation with these antioxidants offers a means to inhibit multiple hyperglycemia-induced retinal metabolic abnormalities. 相似文献
12.
Vinícius Stone Pauline M. August Daniela P. Stocher Caroline P. Klein Pablo R. G. Couto Yasmini D. Silva 《Free radical research》2016,50(5):530-541
Dietary restriction increases life span and protects distinct organisms against a series of diseases, among which, those related to oxidative stress, like neurodegenerative diseases. Interferences in the maternal environment are known to reprogram the offspring metabolism response, impacting in the risk of chronic diseases development in adulthood. We aimed to assess the effects of 40% food restriction on reactive species levels, enzymatic and non-enzymatic antioxidant defenses, and oxidative damage parameters in the cerebellum and total cerebral cortex of pregnant rats and their offspring. Dams and pups showed oxidative modulation caused by food restriction in both structures. Dichlorofluorescein oxidation, reflecting reactive species levels, was reduced in the cerebellum of dams and offspring, while the cerebral cortex was not affected. Decreased mitochondrial superoxide levels were found in the cerebellum and cerebral cortex of pups, while nitric oxide was increased in the cortex. We also measured the activities of important antioxidant enzymes responsible by reactive oxygen species elimination. Superoxide dismutase activity was increased in the cerebellum of dams and in both structures of pups, while it was decreased in dams’ cerebral cortex. Both brain structures were affected concerning to catalase, glutathione peroxidase, and glutaredoxin activities, which were reduced in pups and dams. Non-enzymatic defenses were decreased in pups, while dams showed an adaptive pattern in the cerebellum and no alteration in the cerebral cortex. Even though the results suggest increased oxidative status, lipids and proteins were not oxidatively affected. Our data suggest that intrauterine food restriction may disrupt oxidative status, impairing the antioxidant network. 相似文献
13.
Feksa LR Latini A Rech VC Wajner M Dutra-Filho CS de Souza Wyse AT Wannmacher CM 《Neurochemistry international》2006,49(1):87-93
Despite the significant brain abnormalities, the neurotoxic mechanisms of brain injury in hypertryptophanemia are virtually unknown. In this work, it was investigated the in vitro effect of l-tryptophan on various parameters of oxidative stress, namely spontaneous chemiluminescence, thiobarbituric acid-reactive substances (TBA-RS), total radical-trapping antioxidant potential (TRAP), total antioxidant reactivity (TAR) and glutathione (GSH) levels in cerebral cortex from 30-day-old rats. Tryptophan significantly increased chemiluminescence and TBA-RS measurements indicating that this amino acid induced lipid peroxidation in vitro. We also observed that tryptophan significantly decreased the brain antioxidant defenses by reducing the values of TRAP, TAR and GSH, reflecting that the overall content of antioxidants was reduced by tryptophan. Furthermore, the tryptophan-induced increase of TBA-RS was fully prevented by GSH and by combination of catalase plus superoxide dismutase, but not by the inhibitor of nitric oxide synthase N(omega)-nitro-L-arginine methyl ester (L-NAME). In case these findings also occur in human hypertryptophanemia or in other neurodegenerative diseases in which tryptophan accumulates, it is feasible that oxidative stress may be involved in the mechanism leading to the brain injury observed in patients affected by these disorders. 相似文献
14.
Dose dependent effects of ghrelin on pentylenetetrazole-induced oxidative stress in a rat seizure model 总被引:3,自引:0,他引:3
It has been suggested that free oxygen radicals play a role in the genesis of epilepsy and in post-seizure neuronal death. The aim of this study was to investigate the dose dependent effect of ghrelin on pentylenetetrazole (PTZ)-induced oxidative stress in a rat seizure model. For this purpose, the ghrelin groups were treated with intraperitoneal injections of ghrelin at doses of 20, 40, 60 and 80 microg/kg before the PTZ injection. Superoxide dismutase (SOD) and catalase (CAT) activities, and reduced glutathione (GSH) and thiobarbituric acid-reactive substance (TBARS) levels were measured in erythrocytes, liver and brain tissue. TBARS, the indicator of lipid peroxidation, was significantly increased in erythrocytes, liver and brain tissue, while antioxidant enzyme activities and glutathione levels were significantly decreased in PTZ injected rats. Ghrelin pretreatment prevented lipid peroxidation and the reduction in antioxidant enzyme activities and GSH levels against PTZ-induced oxidative stress in a dose dependent manner. The present data indicates that PTZ at a convulsive dose induces an oxidative stress response by depleting the antioxidant defense systems and increasing lipid peroxidation in the erythrocytes, liver and brain of rats. Ghrelin pretreatment diminished oxidative stress and prevented the decrease in antioxidant enzyme activities, and thus may reduce neuronal death in the brain during seizures. However, further studies are needed in order to confirm our hypothesis. 相似文献
15.
16.
Sathyasaikumar KV Swapna I Reddy PV Murthy ChR Dutta Gupta A Senthilkumaran B Reddanna P 《Neurochemical research》2007,32(3):517-524
Hepatic Encephalopathy (HE) is one of the most common complications of acute liver diseases and is known to have profound
influence on the brain. Most of the studies, available from the literature are pertaining to whole brain homogenates or mitochondria.
Since brain is highly heterogeneous with functions localized in specific areas, the present study was aimed to assess the
oxidative stress in different regions of brain-cerebral cortex, cerebellum and pons medulla during acute HE. Acute liver failure
was induced in 3-month old adult male Wistar rats by intraperitoneal injection of thioacetamide (300 mg/kg body weight for
two days), a well known hepatotoxin. Oxidative stress conditions were assessed by free radical production, lipid peroxidation,
nitric oxide levels, GSH/GSSG ratio and antioxidant enzyme machinery in three distinct structures of rat brain-cerebral cortex,
cerebellum and pons medulla. Results of the present study indicate a significant increase in malondialdehyde (MDA) levels,
reactive oxygen species (ROS), total nitric oxide levels [(NO) estimated by measuring (nitrites + nitrates)] and a decrease
in GSH/GSSG ratio in all the regions of brain. There was also a marked decrease in the activity of the antioxidant enzymes-glutathione
peroxidase, glutathione reductase and catalase while the super oxide dismutase activity (SOD) increased. However, the present
study also revealed that pons medulla and cerebral cortex were more susceptible to oxidative stress than cerebellum. The increased
vulnerability to oxidative stress in pons medulla could be due to the increased NO levels and increased activity of SOD and
decreased glutathione peroxidase and glutathione reductase activities. In summary, the present study revealed that oxidative
stress prevails in different cerebral regions analyzed during thioacetamide-induced acute liver failure with more pronounced
effects on pons medulla and cerebral cortex.
Murthy Ch.R.K—Deceased while in service. 相似文献
17.
Levi Raphael Wolf Tamar Fleminger Gideon Solomon Beka 《Molecular and cellular biochemistry》1998,178(1-2):41-46
Studies were conducted to ascertain any involvement of free radical mediated prooxidative processes in different brain regions following diazopam administration. A significant decrease in TBA reactive substance formation was observed in cerebral cortex, cerebellum and brain stem regions after single doses of 1.5, 3 and 6 mg/kg b.wt. For further studies rats were given diazepam (i.p.) at 3 mg/kg body weight dose and sacrificed after 1 h to follow changes in the pro/antioxidant status. An enhancement in the TBARS formation was found in the mitochondrial fractions from cerebral cortex and brain stem. This effect was highest in brain stem being 107% as compared to controls. In the post mitochondrial fraction, cerebellum showed 49% enhancement whereas decreased formation of thiobarbituric acid reactive substances was observed in cerebral cortex and brain stem. Isozymes of superoxide dismutase showed a decrease in activity which was region dependent. Even though, total thiols were not significantly altered, free thiols showed depletion in cerebellum (39.8%) and brain stem (50%). Glutathione reductase activity was also decreased in cerebellum and brain stem. The results indicate that a single dose of diazepam causes free radical mediated changes and the modulatory response of antioxidant defences appears to be region specific. 相似文献
18.
Schuck PF Ceolato PC Ferreira GC Tonin A Leipnitz G Dutra-Filho CS Latini A Wajner M 《Free radical research》2007,41(11):1261-1272
Patients affected by medium-chain acyl-CoA dehydrogenase deficiency (MCADD) suffer from acute episodes of encephalopathy whose underlying mechanisms are poorly known. The present work investigated the in vitro effect of cis-4-decenoic acid (cDA), which accumulates in MCADD, on important parameters of oxidative stress in cerebral cortex of young rats. cDA markedly induced lipid peroxidation, as verified by the increased levels of spontaneous chemiluminescence and thiobarbituric acid-reactive substances. Furthermore, cDA significantly increased carbonyl formation and sulphydryl oxidation, which is indicative of protein oxidative damage, and promoted 2',7'-dihydrodichlorofluorescein oxidation. It was also observed that the non-enzymatic tissue antioxidant defenses were decreased by cDA, whereas the antioxidant enzyme activities catalase, superoxide dismutase and glutathione peroxidase were not altered. Moreover, cDA-induced lipid peroxidation and GSH reduction was totally blocked by free radical scavengers, suggesting that reactive species were involved in these effects. The data indicate that oxidative stress is induced by cDA in rat brain in vitro and that oxidative damage might be involved in the pathophysiology of the encephalopathy in MCADD. 相似文献
19.
Latini A Ferreira GC Scussiato K Schuck PF Solano AF Dutra-Filho CS Vargas CR Wajner M 《Cellular and molecular neurobiology》2007,27(4):423-438
1. Glutaric acidemia type I (GA I) is a neurometabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase, which
leads to tissue accumulation of predominantly glutaric acid (GA) and also 3-hydroxyglutaric acid to a lesser amount. Affected
patients usually present progressive cortical atrophy and acute striatal degeneration attributed to the toxic accumulating
metabolites.
2. In the present study, we determined a number of oxidative stress parameters, namely chemiluminescence, thiobarbituric acid-reactive
substances (TBA-RS), total antioxidant reactivity (TAR), glutathione (GSH) levels, and the activities of catalase and glutathione
peroxidase (GPx), in various tissues from rats chronically exposed to GA or to saline (controls). High GA concentrations,
similar to those found in glutaric aciduria type I, were induced in the brain by three daily subcutaneous injections of saline-buffered
GA (5 μmol/g body weight) to Wistar rats of 5–22 days of life. The parameters were assessed 12 h after the last GA administration
in different brain structures, skeletal muscle, heart, liver, erythrocytes, and plasma. The lipid peroxidation parameters
chemiluminescence and/or TBA-RS measurements were found significantly increased in midbrain, liver, and erythrocytes of GA-injected
rats. The activity of GPx was significantly reduced in midbrain and markedly increased in liver. TAR measurement was significantly
reduced in midbrain and liver. Furthermore, GSH levels were reduced in liver and heart.
We also investigated the acute in vivo effect of GA administration on the same oxidative stress parameters in cerebral structures and erythrocytes from 22-day-old
rats. We found that TBA-RS values were significantly increased in erythrocytes, TAR levels were markedly decreased in midbrain
and cerebellum, and GPx activity mildly reduced in the midbrain.
3. These data showing an imbalance between antioxidant defences and oxidative damage, particularly in midbrain, liver, and
erythrocytes from GA-injected rats, indicate that oxidative stress might be involved in GA toxicity and that the midbrain,
where the striatum is located, is the brain structure more susceptible to GA chronic and acute exposition. 相似文献
20.
Patrícia Fernanda Schuck Estela Natacha Brandt Busanello Alana Pimentel Moura Anelise Miotti Tonin Mateus Grings Luciana Ritter Carmen Regla Vargas Gustavo da Costa Ferreira Moacir Wajner 《Neurochemical research》2010,35(2):298-305
High concentrations of ethylmalonic acid are found in tissues and biological fluids of patients affected by ethylmalonic encephalopathy,
deficiency of short-chain acyl-CoA dehydrogenase activity and other illnesses characterized by developmental delay and neuromuscular
symptoms. The pathophysiological mechanisms responsible for the brain damage in these patients are virtually unknown. Therefore,
in the present work we investigated the in vitro effect of EMA on oxidative stress parameters in rat cerebral cortex. EMA
significantly increased chemiluminescence and thiobarbituric acid-reactive species levels (lipoperoxidation), as well as carbonyl
content and oxidation of sulfhydryl groups (protein oxidative damage) and DCFH. EMA also significantly decreased the levels
of reduced glutathione (non-enzymatic antioxidant defenses). In contrast, nitrate and nitrite levels were not affected by
this short organic acid. It is therefore presumed that oxidative stress may represent a pathomechanism involved in the pathophysiology
of the neurologic symptoms manifested by patients affected by disorders in which EMA accumulates. 相似文献