Sub­chronic administration of lead alters markers of oxidative stress, acetylcholinesterase and Na+K+­ATPase activities in rat brain.

This study investigated the effects of sub­chronic administration of lead (Pb) acetate on thiobarbituric acid reactive substances (TBA­RS), total sulfhydryl content, protein carbonyl content, antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GSH­Px]), acetylcholinesterase (AChE), and Na+K+­ATPase in the cerebral structures of rats. Male Wistar rats aged 60 days were treated with saline (control group) or Pb (treatment group), at various doses, by gavage, once a day for 35 days. The animals were sacrificed twelve hours after the last administration, and the cerebellum, hippocampus and cerebral cortex were removed. The results showed that Pb did not alter the evaluated oxidative stress parameters. Furthermore, Pb (64 and/or 128 mg/kg) altered SOD in the cerebellum, cerebral cortex and hippocampus. Pb (128 mg/kg) altered CAT in the cerebellum and cerebral cortex and GSH­Px in the cerebral cortex. Also, Pb (64 mg/kg and 128 mg/kg) altered GSH­Px in the cerebellum. Moreover, Pb (128 mg/kg) increased AChE in the hippocampus and decreased Na+K+­ATPase in the cerebellum and hippocampus. In conclusion, sub­chronic exposure to Pb (occupational and environmental intoxication) altered antioxidant enzymes, AChE, and Na+K+­ATPase, contributing to cerebral dysfunction.

In vitro galactose impairs energy metabolism in the brain of young rats: protective role of antioxidants.

We, herein, investigated the in vitro effects of galactose on the activity of pyruvate kinase, succinate dehydrogenase (SDH), complex II and IV (cytochrome c oxidase) of the respiratory chain and Na+K+-ATPase in the cerebral cortex, cerebellum and hippocampus of 30-day-old rats. We also determined the influence of the antioxidants, trolox, ascorbic acid and glutathione, on the effects elicited by galactose. Galactose was added to the assay at concentrations of 0.1, 3.0, 5.0 and 10.0 mM. Control experiments were performed without galactose. Galactose, at 3.0, 5.0 and 10.0 mM, decreased pyruvate kinase activity in the cerebral cortex and at 10.0 mM in the hippocampus. Galactose, at 10.0 mM, reduced SDH and complex II activities in the cerebellum and hippocampus, and reduced cytochrome c oxidase activity in the hippocampus. Additionally, decreased Na+K+-ATPase activity in the cerebral cortex and hippocampus; conversely, galactose, at 3.0 and 5.0 mM, increased this enzyme's activity in the cerebellum. Data show that galactose disrupts energy metabolism and trolox, ascorbic acid and glutathione addition prevented the majority of alterations in the parameters analyzed, suggesting the use of antioxidants as an adjuvant therapy in Classic galactosemia.

Concepts of Neuroinflammation and Their Relationship With Impaired Mitochondrial Functions in Bipolar Disorder.

Bipolar disorder (BD) is a chronic psychiatric disease, characterized by frequent behavioral episodes of depression and mania, and neurologically by dysregulated neurotransmission, neuroplasticity, growth factor signaling, and metabolism, as well as oxidative stress, and neuronal apoptosis, contributing to chronic neuroinflammation. These abnormalities result from complex interactions between multiple susceptibility genes and environmental factors such as stress. The neurocellular abnormalities of BD can result in gross morphological changes, such as reduced prefrontal and hippocampal volume, and circuit reorganization resulting in cognitive and emotional deficits. The term "neuroprogression" is used to denote the progressive changes from early to late stages, as BD severity and loss of treatment response correlate with the number of past episodes. In addition to circuit and cellular abnormalities, BD is associated with dysfunctional mitochondria, leading to severe metabolic disruption in high energy-demanding neurons and glia. Indeed, mitochondrial dysfunction involving electron transport chain (ETC) disruption is considered the primary cause of chronic oxidative stress in BD. The ensuing damage to membrane lipids, proteins, and DNA further perpetuates oxidative stress and neuroinflammation, creating a perpetuating pathogenic cycle. A deeper understanding of BD pathophysiology and identification of associated biomarkers of neuroinflammation are needed to facilitate early diagnosis and treatment of this debilitating disorder.

Protective effect of resveratrol on citrullinemia type I-induced brain oxidative damage in male rats.

Citrullinemia Type I is an inborn error, which leads to accumulation of citrulline and ammonia in blood and body tissues. We evaluated the in vitro effects of citrulline, ammonia and the influence of resveratrol on oxidative stress parameters in the cerebrum of 30- and 60-day-old male Wistar rats. Citrulline (0.1, 2.5, 5.0 mM), ammonia (0.01, 0.1, 1.0 mM) and resveratrol (0.01, 0.1, 0.5 mM) were added to the assays to measure thiobarbituric acid reactive substances (TBA-RS), total sulfhydryl content and the activity of antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Citrulline (2.5 and 5.0 mM) increased TBA-RS in the cerebellum of 30-day-old and in the cerebral cortex and cerebellum of 60-day-old. Citrulline (5.0 mM) increased SOD and reduced GSH-Px in the hippocampus of 30-day-old, whereas in the cerebellum it increased GSH-Px. In the cerebral cortex, 2.5 and 5.0 mM citrulline reduced GSH-Px. In 60-day-old, 2.5 and 5.0 mM citrulline increased SOD in the cerebellum, increased GSH-Px in the cerebral cortex and 5.0 mM citrulline reduced CAT and increased SOD in the cerebral cortex. Ammonia (0.1 and 1.0 mM) reduced the sulfhydryl content in the cerebral cortex of 30- and 60-day-old, 1.0 mM ammonia increased SOD and reduced GSH-Px in the cerebellum of 30-day-old and increased SOD in the hippocampus and cerebellum of 60-day-old. Resveratrol was able to prevent the majority of these alterations. Thus, citrulline and ammonia induce oxidative stress in the cerebrum of rats; however, resveratrol was able to exert antioxidant effects against these substances.

Effects of resveratrol on alterations in cerebrum energy metabolism caused by metabolites accumulated in type I citrullinemia in rats.

We investigated the in vitro effects of citrulline (0.1, 2.5 and 5.0 mM) and ammonia (0.01, 0.1 and 1.0 mM), and the influence of resveratrol (0.01 mM, 0.1 mM and 0.5 mM) on pyruvate kinase, citrate synthase, succinate dehydrogenase (SDH), complex II, and cytochrome c oxidase activities in cerebral cortex, cerebellum and hippocampus homogenates of 60-day-old male Wistar rats. Results showed that 2.5 and 5.0 mM citrulline decreased pyruvate kinase activity in cerebral cortex and, at a concentration of 5.0 mM, increased its activity in hippocampus. Additionally, 5.0 mM citrulline increased citrate synthase activity in the cerebellum of rats. Citrulline (5.0 mM) reduced complex II and cytochrome c oxidase activities in cerebral cortex and hippocampus. With regard to ammonia, at 0.1 and 1.0 mM, decreased complex II activity in cerebral cortex and at 1.0 mM decreased its activity in cerebellum and hippocampus. Ammonia (1.0 mM) also decreased cytochrome c oxidase activity in cerebral cortex and cerebellum of rats. Resveratrol was able to prevent most of the alterations caused by these metabolites in the biomarkers of energy metabolism measured in the cerebrum of rats. Data suggest that these alterations in energy metabolism, caused by citrulline and ammonia, are probably mediated by the generation of free radicals, which can in turn be scavenged by resveratrol.

Hypolipidemic, hipoglycemiant and antioxidant effects of Myrcia splendens (Sw) DC in an animal type 2 diabetes model induced by streptozotocin / Efectos hipolipemiante, hipoglucemiante y antioxidante de Myrcia splendens (Sw) DC en un modelo animal de diabetes tipo 2 inducido por estreptozotocina

We investigated the effects of dichloromethane extract (DME) from Myrcia splendenson alterations caused by type 2 diabetes in the blood and kidney of rats, in order to reduce side effects caused by synthetic drugs. Rats received streptozotocin (60 mg/kg),15 minutes after nicotinamide (120 mg/kg) or water. After 72 hours, the glycemic levels were evaluated to confirm diabetes and the animals received (15 days) DME (25, 50, 100 or 150 mg/Kg) or water. DME partially reversed hyperglycemia and (100 and 150 mg/kg) reversed hypertriglyceridemia. Histopathological findings elucidated that DME reduced damage to pancreatic islets. DME 150 mg/kgreversed the increases in TBA-RS, the reduction in the sulfhydryl content, 100 and 150 mg/kg increased CAT, reversed the decrease in GSH-Px and increased it activity in the blood. DME 150 mg/kg reversed CAT and GSH-Px reductions in the kidney. We believe that DME effects might be dependent on the presence of phenolic compounds.

Investigamos los efectos del extracto de diclorometano (DME)de Myrcia splendens sobre las alteraciones causadas por la diabetes tipo 2 en la sangre y los riñones de las ratas, para reducir los efectos secundarios causados por las drogas sintéticas. Las ratas recibieron estreptozotocina (60 mg/kg), 15 minutos después de la nicotinamida (120 mg/kg) o agua. Después de 72 horas, se confirmo la diabetes y los animales recibieron (15 días) DME (25, 50, 100 o 150 mg/Kg) o agua. DME revierte parcialmente la hiperglucemia y revierte la hipertrigliceridemia. DME redujo el daño a los islotes pancreáticos. DME revirtió los aumentos en TBA-RS, la reducción en el contenido de sulfhidrilo, aumentó la CAT, revirtió la disminución en GSH-Px y aumentó su actividad en la sangre. Además, DME revirtió las reducciones de CAT y GSH-Px en el riñón. Creemos que los efectos provocados por DME pueden depender de la presencia de compuestos fenólicos.

Antioxidant effects on the intracerebroventricular galactose damage in rats.

We investigated the effects of the intracerebroventricular infusion of galactose and the influence of pretreatment with antioxidants on oxidative stress parameters and acethylcholinesterase (AChE) activity in the brain of 60-day-old Wistar rats (6 per group). The animals were divided into naïve group (did not undergo surgery); procedure group (only underwent surgery); sham group (underwent surgery and received 5 µL saline) and galactose group (received 5 µL of galactose solution (5.0 mM) by intracerebroventricular injection), and were killed by decapitation after 1 h. Other groups were pretreated daily for 1 week with saline (sham and galactose groups) or antioxidants, α-tocopherol (40 mg/kg) plus ascorbic acid (100 mg/kg, i.p.) (antioxidants and galactose + antioxidants groups). Twelve hours after the last antioxidants injection, animals received an intracerebroventricular infusion of 5 µL of galactose solution (galactose and galactose + antioxidants groups) or saline (sham and antioxidants groups) and were sacrificed 1 h later. Galactose elevated thiobarbituric acid reactive substances (TBA-RS), protein carbonyl content and glutathione peroxidase (GSH-Px) activity and decreased total sulfhydryl content and catalase (CAT) activity in the cerebral cortex. In the hippocampus, galactose enhanced TBA-RS, decreased total sulfhydryl content and increased AChE activity, while in the cerebellum it decreased total sulfhydryl content and increased CAT and superoxide dismutase (SOD) activities. Pretreatment with antioxidants prevented the majority of these alterations, indicating the participation of free radicals in these effects. Thus, intracerebroventricular galactose infusion impairs redox homeostasis in the brain; the administration of antioxidants should be considered as an adjuvant therapy to specific diets in galactosemia.

Antioxidant and antidepressant-like effects of Eugenia catharinensis D. Legrand in an animal model of depression induced by corticosterone.

This work investigated the antioxidant and antidepressant-like effects of ethyl acetate extract from Eugenia catharinensis in mice treated with corticosterone (20 mg/Kg). The animals received saline or corticosterone (21 days) and, in the last 7 days, they were treated with the extract (50, 125, 200 or 250 mg/Kg) or vehicle. After 24 h, the mice were submitted to the open field and forced swimming tests, after which the hippocampus and cerebral cortex were removed. Our results showed that the extract decreased the immobility time of mice in the forced swimming test and that the extract was able to reverse the effect caused by corticosterone. Corticosterone pre-treatment generated oxidative stress, altering antioxidant enzymes in the nervous tissue. The extract increased the catalase and superoxide dismutase activities and reversed the effects of corticosterone. In the hippocampus, the extract increased superoxide dismutase activity and reversed the increase in catalase activity elicited by corticosterone. We propose that the effects elicited by the Eugenia catharinensis are dependent on the presence of phenolic compounds (gallic acid, protocatechuic acid, syringic acid, 4-hydroxy methylbenzoic acid, chlorogenic acid, salicylic acid, caffeic acid, vanillic acid, p-coumaric acid, isoquercetin, rutin, ferulic acid, aromadendrin, galangin and apigenin) in this extract, as demonstrated by HPLC-ESI-MS/MS.

Effects of two aerobic exercise training protocols on parameters of oxidative stress in the blood and liver of obese rats.

We evaluated the effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) protocols on the alterations in oxidative stress parameters caused by a high-fat diet (HFD), in the blood and liver of rats. The HFD enhanced thiobarbituric acid reactive substances (TBA-RS) and protein carbonyl content, while reducing total sulfhydryl content and catalase (CAT) and glutathione peroxidase (GSH-Px) activities in the blood. Both training protocols prevented an increase in TBA-RS and protein carbonyl content, and prevented a reduction in CAT. HIIT protocol enhanced SOD activity. In the liver, HFD didn't alter TBA-RS, total sulfhydryl content or SOD, but increased protein carbonyl content and CAT and decreased GSH-Px. The exercise protocols prevented the increase in protein carbonyl content and the MICT protocol prevented an alteration in CAT. In conclusion, HFD elicits oxidative stress in the blood and liver and both protocols prevented most of the alterations in the oxidative stress parameters.

Hypolipemiant and antioxidant effects of Eugenia brasiliensis in an animal model of coconut oil-induced hypertriglyceridemia.

We investigated the effects of chronic administration of crude hydroalcoholic extract (CHE) and crude acetone extract (CAE) obtained from leaves of Eugenia brasiliensis species on hypertriglyceridemia and oxidative stress caused by the chronic administration of coconut oil. Rats received CHE or CAE (50, 100 or 150mg/kg, orally) for 30days, plus coconut oil (2mL, orally) or saline for 15th. Triglyceride levels, liver cell lipid accumulation, thiobarbituric acid reactive substances (TBA-RS), total sulfhydryl content and the activities of antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were evaluated in the blood and liver of rats. Results showed that chronic administration of CHE or CAE was able to prevent hypertriglyceridemia and decrease the lipid droplets in liver cells, as well as the increase in TBA-RS, the reduction in total sulfhydryl content and CAT activity in the blood and prevent total or partial the increase in CAT and reduction in SOD and GSH-Px activities in the liver. These findings indicate that both extracts may have hypolipidemic and antioxidant effects.

Cocoa and classical music: effect on anxiety and antioxidant activity in Wistar rats / Cacao y música clásica: efecto sobre ansiedad y actividad antioxidante en ratas Wistar

The effect of cocoa powder and subchronic exposure to classical music in Wistar rats behavior on anxiety evaluation tests and their antioxidant activity was evaluated. The animals were divided into four groups: control group (CG), cocoa powder group (CPG), music group (MG) and cocoa powder with music group (CPMG). During 15 days, CPG and CPMG received commercial non-alkalized cocoa powder daily (66 mg total polyphenols / g of product, by oral gavage), while MG and CPMG were exposed to the music of Mozart (Serenade N.10 in B flat major for woodwinds and bass, "Gran partita" K.361 / 370a, Largo movement, 8:35 minutes long). At the end of the experiment, the animals were submitted to elevated plus-maze (EPM) and openfield (OF) tests, and serum analysis of thiobarbituric acid reactive substances index (TBA-RS) and the activity of antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Animals from MG and CPMG groups showed the highest total horizontal locomotion and more time spent at the central area and reduced immobility time at the OF. The TBA-RS average of the treated groups were lower than the GC. The average activity of CAT was higher in CPMG than the others, and the average activity of SOD and GSH-Px were higher only in CPG and CPMG. We concluded that the treatment with this classical music showed mild anxiolytic activity. Both treatments (cocoa and music) improved serum antioxidant status, but the peripheral activity of different serum enzymes was mainly improved by the cocoa powder(AU)

Se evaluó el efecto de cacao en polvo y la exposición subcrónica a la música clásica sobre el comportamiento de ratas Wistar en pruebas de evaluación de la ansiedad y su actividad antioxidante. Los animales fueron divididos en cuatro grupos: control (GC), cacao en polvo (GCP), música (GM) y cacao en polvo con música (GCPM). Durante 15 días, GCP y GCPM recibieron cacao en polvo comercial no alcalinizado diariamente (66 mg de polifenoles totales / g de producto, mediante una sonda nasogástrica), mientras que GM y GCPM fueron expuestos a la música de Mozart (Serenata N.10 em Si bemol mayor, "Gran Partita" K.361 / 370a, movimiento Largo, 8:35 minutos de duración). Al final del experimento, los animales fueron sometidos a las pruebas de laberinto en cruz elevado (LCE) y de campo abierto (CA), y el análisis sérica del índice de sustancias reactivas al ácido tiobarbitúrico (TBA-RS) y la actividad de las enzimas antioxidantes catalasa (CAT), superóxido dismutasa (SOD) y glutatión peroxidasa (GSH-Px). Los animales GM y GCPM mostraron la mayor locomoción horizontal, más tiempo en la zona central y un tiempo reducido de inmovilidad en el CA. El TBA-RS promedio de los grupos tratados fue más bajo que el control. La actividad media de CAT fue mayor para GCPM que los otros, y la actividad media de la SOD y GSH-Px fueron mayores sólo en GCP y GCPM. Concluimos que el tratamiento con esta música clásica mostró modesta actividad ansiolítica. Ambos tratamientos (cacao y música) mejoraron el estado antioxidante en suero, pero la actividad periférica de diferentes enzimas fue mejorada principalmente por acción del cacao(AU)

Argininic acid alters markers of cellular oxidative damage in vitro: Protective role of antioxidants.

We, herein, investigated the in vitro effects of argininic acid on thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content and on the activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the blood, kidney and liver of 60-day-old rats. We also verified the influence of the antioxidants (each at 1.0mM) trolox and ascorbic acid, as well as of NG-nitro-l-arginine methyl ester (L-NAME) at 1.0mM, a nitric oxide synthase inhibitor, on the effects elicited by argininic acid on the parameters tested. The liver, renal cortex and renal medulla were homogenized in 10vol (1:10w/v) of 20mM sodium phosphate buffer, pH 7.4, containing 140mM KCl; and erythrocytes and plasma were prepared from whole blood samples obtained from rats. For in vitro experiments, the samples were pre-incubated for 1h at 37°C in the presence of argininic acid at final concentrations of 0.1, 1.0 and 5.0µM. Control experiments were performed without the addition of argininic acid. Results showed that argininic acid (5.0µM) enhanced CAT and SOD activities and decreased GSH-Px activity in the erythrocytes, increased CAT and decreased GSH-Px activities in the renal cortex and decreased CAT and SOD activities in the renal medulla of 60-day-old rats, as compared to the control group. Antioxidants and/or L-NAME prevented most of the alterations caused by argininic acid on the oxidative stress parameters evaluated. Data suggest that argininic acid alters antioxidant defenses in the blood and kidney of rats; however, in the presence of antioxidants and L-NAME, most of these alterations in oxidative stress were prevented. These findings suggest that oxidative stress may be make an important contribution to the damage caused by argininic acid in hyperargininemic patients and that treatment with antioxidants may be beneficial in this pathology.

The effect of d-galactose induced oxidative stress on in vitro redox homeostasis in rat plasma and erythrocytes.

We, herein, investigated the in vitro effects of galactose on thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content, and on the activities of antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and butyrylcholinesterase (BuChE) in the blood of 30- and 60-day-old rats. We also determined the influence of the antioxidants, trolox, ascorbic acid and glutathione, on the effects elicited by galactose on the parameters tested. Galactose was added to the assay at final concentrations of 0.1, 3.0, 5.0 and 10.0mM. Control experiments were performed without the addition of galactose. Rats were sacrificed by decapitation without anesthesia and a blood sample was removed for analysis. Galactose, at 3.0mM, 5.0mM and 10.0mM, enhanced TBA-RS in the plasma of 60-day-old rats, while 10.0mM galactose reduced total sulfhydryl content in the plasma of 30-day-old rats; 5.0mM and 10.0mM galactose enhanced CAT activity in the erythrocytes of 30- and 60-day-old rats and 10.0mM galactose reduced SOD activity in the erythrocytes of 60-day-old rats. Galactose did not alter BuChE activity. Data showed that at the pathologically high concentration (greater than 5.0mM), galactose induces lipid peroxidation, reduces total sulfhydryl content and alters antioxidant defenses in the blood of rats. Trolox, ascorbic acid and glutathione addition prevented most alterations in oxidative stress parameters that were caused by galactose. Our findings lend support to a potential therapeutic strategy for this disease, which may include the use of antioxidants for ameliorating the damage caused by galactose.

Galactose alters markers of oxidative stress and acetylcholinesterase activity in the cerebrum of rats: protective role of antioxidants.

We evaluated the in vitro effects of galactose at 0.1, 3.0, 5.0 and 10.0 mM on thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content, protein carbonyl content, on the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and on acetylcholinesterase (AChE) activity in the cerebral cortex, cerebellum and hippocampus of rats. We also investigated the influence of the antioxidants (each at 1 mM), α-tocopherol, ascorbic acid and glutathione, on the effects elicited by galactose on the parameters tested. Results showed that galactose, at a concentration of 3.0 mM, enhanced TBA-RS levels in the hippocampus, cerebral cortex and cerebellum of rats. In the cerebral cortex, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS and protein carbonyl content, and at 10.0 mM increased CAT activity and decreased AChE activity. In the cerebellum, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS, SOD and GSH-Px activities. In the hippocampus, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS and CAT activity and at 10.0 mM decreased GSH-Px. Data showed that at the pathologically high concentration (greater than 5.0 mM), galactose induces lipid peroxidation, protein carbonylation, alters antioxidant defenses in the cerebrum, and also alters cholinesterase activity. Trolox, ascorbic acid and glutathione addition prevented the majority of alterations in oxidative stress parameters and the decrease in AChE activity that were caused by galactose. Our findings lend support to a potential therapeutic strategy for this condition, which may include the use of appropriate antioxidants for ameliorating the damage caused by galactose.

Hyperargininemia and renal oxidative stress: Prevention by antioxidants and NG -nitro-l-arginine methyl ester.

We investigated the in vitro and in vivo effects of arginine (Arg) on thiobarbituric acid-reactive substances (TBA-RS) and on the activities of catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) in renal tissues of rats. We also studied the influence of antioxidants (α-tocopherol plus ascorbic acid) and nitric oxide synthase inhibitor NG -nitro-l-arginine methyl ester (l-NAME) on the effects elicited by Arg. Results showed that Arg in vitro (1.5 mM) decreased SOD activity and increased the levels of TBA-RS in the renal medulla. Acute administration of Arg [0.8 g/kg, intraperitoneal injection] decreased CAT activity, increased SOD activity and TBA-RS levels in the renal medulla, and decreased CAT activity in the renal cortex of rats. Most results were prevented by antioxidants and/or l-NAME. Data indicate that Arg causes an oxidative imbalance in the renal tissues studied; however, in the presence of antioxidants and l-NAME, some of these alterations in oxidative stress were prevented.

Protective effect of green tea extract against proline-induced oxidative damage in the rat kidney.

We investigated, in vivo (acute and chronic), the effects of proline on thiobarbituric acid-reactive substances (TBA-RS) and on the activities of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in renal tissues (cortex and medulla) of rats. For acute administration, 29-day-old rats received a single subcutaneous injection of proline (18.2µmol/g body weight) or an equivalent volume of 0.9% saline solution and were sacrificed 1h later. For chronic treatment, proline was injected subcutaneously in the rats twice a day from the 6th to the 28th day of age, and the animals were killed 12h after the last injection. The results showed that acute administration of proline enhanced CAT, SOD and GSH-Px activities, as well as, TBARS in the cortex and decreased CAT activity in the medulla, while chronic treatment increased the activities of SOD in the cortex and increased CAT, SOD and GSH-Px in the medulla of rats. Furthermore, the green tea extract treatment for one week or from the 6th to the 28th day of age prevented the alterations caused by acute and chronic, respectively, proline administration. Herein, we demonstrated that proline alters antioxidant defenses and induces lipid peroxidation in the kidney of rats and the green tea extract was capable to counteract the proline-induced alterations.

Effect of N-acetylarginine, a metabolite accumulated in hyperargininemia, on parameters of oxidative stress in rats: protective role of vitamins and L-NAME.

In the present investigation, we initially evaluated the in vitro effect of N-acetylarginine on thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content and on the activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the blood, kidney and liver of rats. Results showed that N-acetylarginine, at a concentration of 5.0 µM, decreased the activity of CAT in erythrocytes, enhanced TBA-RS in the renal cortex, decreased CAT and SOD activities in the renal medulla and decreased CAT and increased SOD and GSH-Px activities in the liver of 60-day-old rats. Furthermore, we tested the influence of the antioxidants, trolox and ascorbic acid, as well as of the N(ω) -nitro-L-arginine methyl ester (L-NAME) on the effects elicited by N-acetylarginine on the parameters tested. Antioxidants and L-NAME prevented most of the alterations caused by N-acetylarginine on the oxidative stress parameters evaluated. Data indicate that oxidative stress induction is probably mediated by the generation of NO and/or ONOO(-) and other free radicals because L-NAME and antioxidants prevented the effects caused by N-acetylarginine in the blood, renal tissues and liver of rats. Our findings lend support to a potential therapeutic strategy for this condition, which may include the use of appropriate antioxidants for ameliorating the damage caused by N-acetylarginine.

Effect of hypoxanthine, antioxidants and allopurinol on cholinesterase activities in rats.

In the present study, we investigate the in vitro effect of hypoxanthine on acetylcholinesterase and butyrylcholinesterase activities in the hippocampus, striatum, cerebral cortex and serum of 15-, 30- and 60-day-old rats. Furthermore, we also evaluated the influence of antioxidants, namely α-tocopherol (trolox) and ascorbic acid, and allopurinol to investigate the possible participation of free radicals and uric acid in the effects elicited by hypoxanthine on these parameters. Acetylcholinesterase and butyrylcholinesterase activities were determined according to Ellman et al. (Biochem Pharmacol 7:88-95, 1961), with some modifications. Hypoxanthine (10.0 µM), when added to the incubation medium, enhanced acetylcholinesterase activity in the hippocampus and striatum of 15- and 30-day-old rats and reduced butyrylcholinesterase activity in the serum of 60-day-old rats. The administration of allopurinol and/or antioxidants partially prevented the alterations caused by hypoxanthine in acetylcholinesterase and butyrylcholinesterase activities in the cerebrum and serum of rats. Data indicate that hypoxanthine alters cholinesterase activities, probably through free radicals and uric acid production since the alterations were prevented by the administration of allopurinol and antioxidants. It is presumed that the cholinesterase system may be associated, at least in part, with the neuronal dysfunction observed in patients affected by Lesch-Nyhan disease. In addition, although extrapolation of findings from animal experiments to humans is difficult, it is conceivable that these vitamins and allopurinol might serve as an adjuvant therapy to avoid progression of brain damage in patients affected by this disease.

Mate tea prevents oxidative stress in the blood and hippocampus of rats with acute or chronic ethanol administration.

OBJECTIVE: The aim of this study was to evaluate the influence of acute and chronic intake of mate tea on the effects elicited by acute and chronic administration of ethanol. METHODS: Oxidative stress was evaluated by measuring thiobarbituric acid-reactive substances (TBARS), as well as the activities of the antioxidant enzymes, catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) in the hippocampus and blood of rats. Male Wistar rats were randomly assigned to four groups, for both acute and chronic treatment: (1) control group, (2) treated group, (3) intoxicated group, (4) and intoxicated group treated with mate tea. RESULTS: Both ethanol administrations significantly increased TBARS in plasma and hippocampus of rats and altered antioxidant enzyme activities, changes which were reverted by mate tea administration. CONCLUSIONS: Data indicate that acute and chronic ethanol administration induced oxidative stress in hippocampus and blood and that mate tea treatment was able to prevent this situation.

Guanidino compounds inhibit acetylcholinesterase and butyrylcholinesterase activities: effect neuroprotector of vitamins E plus C.

Hyperargininemia is a metabolic disorder biochemically characterized by tissue accumulating of arginine and other guanidino compounds. Convulsions, lethargy and psychomotor delay or cognitive deterioration are predominant clinical features of this disease. Although neurologic symptoms predominate in this disorder, their pathophysiology is still unknown. In the present study we initially investigated the in vitro effect of arginine, homoarginine, N-acetylarginine and argininic acid on acetylcholinesterase and butyrylcholinesterase in hippocampus and serum of 15-, 30- and 60-day-old rats. Results showed that arginine in vitro significantly decreased acetylcholinesterase activity in hippocampus of 15-day-old rats and increased this enzyme activity in hippocampus of 60-day-old rats, homoarginine and N-acetylarginine significantly increased acetylcholinesterase activity both in hippocampus of 15- and 30-day-old rats. On the other hand, butyrylcholinesterase was inhibited by homoarginine in serum of 15-day-old rats. The influence of the antioxidants trolox and ascorbic acid on the effects elicited by arginine, homoarginine and N-acetylarginine was also studied. Results showed that these antioxidants were able to prevent the alteration on acetylcholinesterase and butyrylcholinesterase activities caused by guanidine compounds studied, suggesting that alterations on these cholinesterases were probably mediated by free radicals. It is presumed that these results might be associated, at least in part, with the neuronal dysfunction of patients affected by hyperargininemia.