Bruna de Souza

Harmine and imipramine promote antioxidant activities in prefrontal cortex and hippocampus

A growing body of evidence has suggested that reactive oxygen species (ROS) may play an important role in the physiopathology of depression. Evidence has pointed to the β-carboline harmine as a potential therapeutic target for the treatment of depression. The present study we evaluated the effects of acute and chronic administration of harmine (5, 10 and 15 mg/kg) and imipramine (10, 20 and 30 mg/kg) or saline in lipid and protein oxidation levels and superoxide dismutase (SOD) and catalase (CAT) activities in rat prefrontal cortex and hippocampus. Acute and chronic treatments with imipramine and harmine reduced lipid and protein oxidation, compared to control group in prefrontal cortex and hippocampus. The SOD and CAT activities increased with acute and chronic treatments with imipramine and harmine, compared to control group in prefrontal cortex and hippocampus. In conclusion, our results indicate positive effects of imipramine antidepressant and β-carboline harmine of oxidative stress parameters, increasing SOD and CAT activities and decreasing lipid and protein oxidation.

Animal model of mania induced by ouabain: Evidence of oxidative stress in submitochondrial particles of the rat brain

The intracerebroventricular (ICV) administration of ouabain (a Na(+)/K(+)-ATPase inhibitor) in rats has been suggested to mimic some symptoms of human bipolar mania. Clinical studies have shown that bipolar disorder may be related to mitochondrial dysfunction. Herein, we investigated the behavioral and biochemical effects induced by the ICV administration of ouabain in rats. To achieve this aim, the effects of ouabain injection immediately after and 7 days following a single ICV administration (at concentrations of 10(-2) and 10(-3)M) on locomotion was measured using the open-field test. Additionally, thiobarbituric acid reactive substances (TBARSs) and superoxide production were measured in submitochondrial particles of the prefrontal cortex, hippocampus, striatum and amygdala. Our findings demonstrated that ouabain at 10(-2) and 10(-3)M induced hyperlocomotion in rats, and this response remained up to 7 days following a single ICV injection. In addition, we observed that the persistent increase in the rat spontaneous locomotion is associated with increased TBARS levels and superoxide generation in submitochondrial particles in the prefrontal cortex, striatum and amygdala. In conclusion, ouabain-induced mania-like behavior may provide a useful animal model to test the hypothesis of the involvement of oxidative stress in bipolar disorder.

Oxidative Stress in Brain According to Traumatic Brain Injury Intensity

BACKGROUND The mechanisms of brain damage and neuroplasticity following traumatic brain injury (TBI) are complex and not completely understood. Thus, we investigated markers of oxidative stress in the central nervous system after mild and severe TBI in rats. MATERIAL AND METHODS Adult male wistar rats (five animals per group) submitted to mild (mTBI group) or severe TBI (sTBI Group) were sacrificed 30 min, 3, 6, or 12 h after the injury to quantify markers of oxidative damage in different brain regions. Levels of thiobarbituric acid reactive species and protein carbonyl in the cortex, hippocampus, striatum, and cerebellum of mTBI and sTBI groups were compared with the control group. RESULTS After mTBI, levels of protein oxidation were increased in all analyzed structures in several different times after injury. The increase in TBARS levels was not so consistent in mTBI. In contrast, sTBI did not induce a sustainable increase in oxidative damage markers in all analyzed structures. CONCLUSIONS Oxidative damage seemed to be inversely proportional to severity of traumatic brain injury.

Effects of cannabidiol on amphetamine-induced oxidative stress generation in an animal model of mania:

Cannabidiol (CBD), a Cannabis sativa constituent, may present a pharmacological profile similar to mood stabilizing drugs, in addition to anti-oxidative and neuroprotective properties. The present study aims to directly investigate the effects of CBD in an animal model of mania induced by d-amphetamine (d-AMPH). In the first model (reversal treatment), rats received saline or d-AMPH (2 mg/kg) once daily intraperitoneal (i.p.) for 14 days, and from the 8th to the 14th day, they were treated with saline or CBD (15, 30 or 60 mg/kg) i.p. twice a day. In the second model (prevention treatment), rats were pretreated with saline or CBD (15, 30, or 60 mg/kg) regime i.p. twice a day, and from the 8th to the 14th day, they also received saline or d-AMPH i.p. once daily. In the hippocampus CBD (15 mg/kg) reversed the d-AMPH-induced damage and increased (30 mg/kg) brain-derived neurotrophic factor (BDNF) expression. In the second experiment, CBD (30 or 60 mg/kg) prevented the d-AMPH-induced formation of carbonyl group in the prefrontal cortex. In the hippocampus and striatum the d-AMPH-induced damage was prevented by CBD (15, 30 or 60 mg/kg). At both treatments CBD did not present any effect against d-AMPH-induced hyperactivity. In conclusion, we could not observe effects on locomotion, but CBD protect against d-AMPH-induced oxidative protein damage and increased BDNF levels in the reversal model and these effects vary depending on the brain regions evaluated and doses of CBD administered.

Efficacy of the combination of N-acetylcysteine and desferrioxamine in the prevention and treatment of gentamicin-induced acute renal failure in male Wistar rats*

BACKGROUND Oxidative stress and the formation of aminoglycoside-iron complexes through iron-dependent Fenton reaction have been proposed to be the major mechanisms in the development of GM-induced acute renal failure (ARF); however, the efficacy of the combination of N-acetylcysteine (NAC) and desferrioxamine (DFX) in the prevention and the treatment of GM-induced ARF has not previously been investigated. METHODS In the prevention protocol, adult male Wistar rats received gentamicin (GM) [70 mg/kg, intraperitoneally (i.p), each 12 h for 7 days], NAC (20 mg/kg, sc, each 8 h for 7 days) and/or DFX (20 mg/kg, sc, at first, fourth and seventh days). In the treatment protocol animals received GM for 7 days. Additionally, animals received NAC and or DFX starting in the fourth day after GM administration. Parameters of renal function had been evaluated 24 h, 4 and 8 days after the beginning of GM administration in the prevention protocol and in Days 5 and 8 in the treatment protocol. At the end of experiment, lipid peroxidation (TBARS assay) and protein oxidation (protein carbonyls levels) formation were evaluated in kidney tissue as oxidative damage parameters. RESULTS In the prevention protocol, GM-induced ARF was prevented by the NAC and DFX association. Lipid peroxidation was attenuated by both antioxidant treatments, but the effects of NAC plus DFX were of greater magnitude. In the treatment protocol, plasma markers of renal injury were improved only in the NAC group, despite the similar antioxidant effect of both NAC, DFX and NAC plus DFX. CONCLUSION Although the combination of NAC and DFX was more effective in the prevention protocol, the use of NAC alone seemed to be superior to NAC-DFX combination, in the treatment of GM-induced ARF in adult male Wistar rats.

Intracerebroventricular ouabain administration induces oxidative stress in the rat brain.

Intracerebroventricular (ICV) injection of ouabain (a potent Na+/K+‐ATPase inhibitor) in rats resulted in manic‐like effects. There is an emerging body of data indicating that major neuropsychiatric disorders, such as bipolar disorder and schizophrenia, are associated with increased oxidative stress. In this study, we investigated the effects of ICV ouabain injection on oxidative stress parameters in total tissue of rat brain. Our findings demonstrated that ICV injection increased thiobarbituric acid reactive species levels and protein carbonyl generation in the prefrontal cortex and hippocampus of rats. Moreover, the activity of the antioxidants enzymes catalase and superoxide dismutase was altered in several areas of the rat brain and cerebrospinal fluid of ICV ouabain‐subjected rats. These results showed that Na+/K+‐ATPase inhibition can lead to oxidative stress in the brain of rats.

N-Methyl-D-Aspartate Glutamate Receptor Blockade Attenuates Lung Injury Associated With Experimental Sepsis

BACKGROUND The aim of this study was to examine the effects of the N-methyl-D-aspartate receptor (NMDAR) channel blocker dizocilpine (MK-801) on lung injury in rats submitted to experimental sepsis induced by cecal ligation and perforation (CLP). METHODS Adult male Wistar rats submitted to CLP were given a single systemic injection of MK-801 (subcutaneously at 0.3 mg/kg) administered 4 or 7 h after CLP induction. Twelve hours after CLP BAL was performed to determine total cell count, protein content, and inflammatory parameters. In addition, lung was excised for histopathologic analyses and determination of NMDAR subunits content. In a separate cohort of animals mortality was recorded for 5 days. RESULTS Animals submitted to sepsis induced by CLP showed an increase in the content of NMDAR subunits NR1 and NR2A in the lung. Administration of MK-801 4 h after CLP induction resulted in a decrease in BAL fluid cellular content and decreased levels of proinflammatory cytokines. In addition, MK-801 decreased lung oxidative stress markers and histopathologic alterations and improved survival. CONCLUSIONS These findings indicate that NMDAR blockade might represent a promising novel therapeutic strategy for the treatment of sepsis and inflammatory disorders.

Effects of acute treatment with amphetamine in locomotor activity in sepsis survivor rats

We here evaluated the central dopaminergic response in sepsis survivor rats using the administration of D-amphetamine. Male Wistar rats underwent cecal ligation and perforation (CLP) or were sham-operated. After 10 days of recovery, rats received an intraperitoneal injection of D-amphetamine 0.5, 1 and 2 mg/kg or saline, and were subjected to the open field test. We did not observe alterations in locomotor and exploratory activities in CLP compared to sham group. Treatment with amphetamine 0.5 mg/kg did not have effect in sham and CLP groups; D-amphetamine 1 mg/kg increased locomotor and exploratory activities only in sham group, and D-amphetamine 2 mg/kg increased in both sham and CLP groups. We suggest that, in part, dopamine pathway may be altered in sepsis.