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Adalisa Reinke

Publications and source records attributed to Adalisa Reinke.

14 recordsLinked to original sources
PubMed2006

Effects of milnacipran in animal models of anxiety and memory.

Serotonin (5-HT) and noradrenaline (NA) are involved in both pathogenesis and recovery from depression and anxiety. We examined the effects of acute and chronic treatment with milnacipran, a serotonin/noradrenaline reuptake inhibitors (SNRIs) antidepressant, on anxiety and memory retention in rats. Male Wistar rats received acute or chronic administration of milnacipran (12.5, 25 or 50 mg/kg) or saline (control group). The animals were separately submitted to elevated plus-maze, inhibitory avoidance and open-field tasks 1 h after injection, in the acute group, or 23 h after last injection, in the chronic group. Our results showed an anxiolytic-like effect after chronic administration of milnacipran at doses of 25 and 50 mg/kg. The treatment does not interfere in memory retention and habituation to a novel environment at any doses studied. These findings support that milnacipran, an established SNRIs antidepressant, can also be useful in the treatment of anxiety disorders.

Animals↗
PubMed2006

Methylphenidate treatment induces oxidative stress in young rat brain.

Methylphenidate (MPH) is frequently prescribed for the treatment of attention deficit/hyperactivity disorder. Psychostimulants can cause long-lasting neurochemical and behavioral adaptations. Here, we evaluated oxidative damage in the rat brain and the differential age-dependent response to MPH after acute and chronic exposure. We investigated the oxidative damage, assessed by the thiobarbituric acid reactive species (TBARS), and the protein carbonyl assays in cerebellum, prefrontal cortex, hippocampus, striatum, and cerebral cortex of young (25 days old) and adult (60 days old) male Wistar rats after acute and chronic exposure to MPH. Chronic MPH-treated young rats presented a dose-dependent increase in TBARS content and protein carbonyls formation in specific rat brain regions. In the acute exposure, only MPH highest dose increased lipid peroxidation in the hippocampus. No difference in protein carbonylation was observed among groups in all structures analyzed. In adult rats, we did not find oxidative damage in both acute and chronic treatment. Chronic exposure to MPH in induces oxidative damage in young rat brain, differentially from chronic exposure during adulthood. These findings highlight the need for further research to improve understanding of MPH effects on developing nervous system and the potential consequences in adulthood resulting from early-life drug exposure.

Age Factors↗
PubMed2006

Effects of N-acetylcysteine plus deferoxamine in lipopolysaccharide-induced acute lung injury in the rat.

OBJECTIVES: Interventions that reduce the generation or the effects of reactive oxygen species exert controversial effects in animal models of lung injury, and these could be secondary to the pro-oxidant effects of antioxidants generally by their interaction with iron. We here describe the effects of N-acetylcysteine, deferoxamine, or both in the treatment of acute lung injury induced by intratracheal lipopolysaccharide injection. DESIGN: Prospective, randomized, controlled experiment. SETTING: Animal basic science laboratory. SUBJECTS: Male Wistar rats, weighing 200-250 g. INTERVENTIONS: Rats exposed intratracheally to lipopolysaccharide were treated with N-acetylcysteine (20 mg/kg subcutaneously 3, 6, and 12 hrs after lipopolysaccharide instillation), deferoxamine (20 mg/kg subcutaneously 3 hrs after lipopolysaccharide instillation), N-acetylcysteine (20 mg/kg, 3, 6, and 12 hrs after lipopolysaccharide instillation) plus deferoxamine (20 mg/kg 3 hrs after lipopolysaccharide instillation), or vehicle. MEASUREMENTS AND MAIN RESULTS: Acute lung injury was induced by intratracheal instillation of lipopolysaccharide in Wistar rats. The animals were randomly divided into five groups: group 1, control with instillation of isotonic saline; group 2, lipopolysaccharide treated with saline; group 3, lipopolysaccharide treated with N-acetylcysteine; group 4, lipopolysaccharide treated with deferoxamine; and group 5, lipopolysaccharide treated with N-acetylcysteine plus deferoxamine. Several times after lipopolysaccharide instillation, the rats were killed and a bronchoalveolar lavage was performed to determine thiobarbituric acid reactive species, protein carbonyls, superoxide dismutase and catalase activities, mitochondrial superoxide production (oxidative stress variables), the degree of the alveolar-capillary membrane compromise, and inflammatory infiltration. Samples from the lung were isolated and assayed for oxidative stress variables or histopathologic analyses. N-acetylcysteine plus deferoxamine decreased bronchoalveolar lavage fluid protein, inflammatory cells, oxidative damage variables, and proinflammatory cytokines. N-acetylcysteine plus deferoxamine treatment significantly attenuated lung oxidative damage, mitochondrial superoxide production, and histopathologic alterations after lipopolysaccharide instillation. CONCLUSIONS: Our data provide the first experimental demonstration that N-acetylcysteine plus deferoxamine decreases oxidative stress and mitochondrial dysfunction and limits inflammatory response and alveolar pathology induced by lipopolysaccharide in the rat.

Acetylcysteine↗
PubMed2006

Oxidative variables in the rat brain after sepsis induced by cecal ligation and perforation.

OBJECTIVE: The underlying mechanisms of the changes in mental status, septic encephalopathy, and long-term cognitive symptoms in sepsis survivors have only been defined in part. The present study was undertaken to assess different variables of oxidative stress in several brain structures after cecal ligation and perforation in the rat. DESIGN: Prospective animal study. SETTING: Animal basic science laboratory. SUBJECTS: Male Wistar rats, weighing 250-350 g. INTERVENTIONS: Rats were subjected to cecal ligation and perforation (sepsis group) with saline resuscitation (at 50 mL/kg immediately and 12 hrs after cecal ligation and perforation) or sham operation (control group). MEASUREMENTS AND MAIN RESULTS: Oxidative damage, assessed by the thiobarbituric acid reactive species and the protein carbonyl assays, occurred early (after 6 hrs) in the course of sepsis development in the hippocampus, cerebellum, and cortex. At longer times after sepsis induction (12-96 hrs), there was no evidence of oxidative damage in all analyzed structures. Except for the striatum, earlier in sepsis development (6 hrs) we demonstrated an increase in superoxide dismutase activity without a proportional increase in catalase activity with a consequent increase in the relation of superoxide dismutase/catalase. The balance between these enzymes was restored in the studied structures 12-96 hrs after sepsis induction. CONCLUSIONS: The short-term oxidative damage demonstrated here could participate in the development of central nervous system symptoms during sepsis development, or even septic encephalopathy. The alterations in the superoxide dismutase/catalase relation were temporally related to the occurrence or not of oxidative damage in the central nervous system.

Animals↗
PubMed2005

Gastrin-releasing peptide receptor antagonist effects on an animal model of sepsis.

RATIONALE: Several new therapeutic strategies have been described for the treatment of sepsis, but to date none are related to alterations in the bombesin/gastrin-releasing peptide (GRP) receptor pathways. OBJECTIVES: To determine the effects of a selective GRP receptor antagonist, RC-3095, on cytokine release from macrophages and its in vivo effects in the cecal ligation and puncture (CLP) model of sepsis and in acute lung injury induced by intratracheal instillation of LPS. METHODS: We determined the effects of RC-3095 in the CLP model of sepsis and in acute lung injury induced by intratracheal instillation of LPS. In addition, we determined the effects of RC-3095 on tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-10, and nitric oxide release from activated macrophages. MEASUREMENTS AND MAIN RESULTS: The GRP antagonist attenuated LPS- or CLP-induced TNF-alpha, IL-1beta, and nitric oxide release in cultured macrophages and decreased the mRNA levels of inducible nitric oxide synthase. The administration of RC-3095 (0.3 mg/kg) 6 h after sepsis induction improved survival in the CLP model, and diminished lung damage after intratracheal instillation of LPS. These effects were associated with attenuation on the circulating TNF-alpha and IL-1beta levels and decreased myeloperoxidase activity in several organs. CONCLUSIONS: We report that a selective GRP receptor antagonist attenuates the release of proinflammatory cytokines in vitro and in vivo and improves survival in "established" sepsis. These are consistent with the involvement of a new inflammatory pathway relevant to the development of sepsis.

Animals↗
PubMed2005

Non-associative learning and anxiety in rats treated with a single systemic administration of the gastrin-releasing peptide receptor antagonist RC-3095.

The gastrin-releasing peptide receptor (GRPR) has been implicated in the modulation of emotionally-motivated memory. In the present study, we investigated the role of the GRPR on non-emotional, non-associative memory, and anxiety. Adult male Wistar rats were given a systemic injection of the GRPR antagonist [D-Tpi6, Leu(13) psi(CH2NH)-Leu14] bombesin (6-14) (RC-3095) (0.2, 1.0 or 5.0mg/kg) 30 min before exposure to an open field or an elevated plus maze. Habituation to the open field was tested in a retention trial carried out 24 h after the first exposure to the open field. Rats given RC-3095 at the doses of 1.0 or 5.0mg/kg showed impaired habituation. Animals treated with 5.0mg/kg of RC-3095 spent significantly more time in the closed arms of the elevated plus maze. No effects of RC-3095 on locomotion or exploratory behavior were observed. The results implicate the GRPR in the regulation of non-emotional, non-associative memory as well as in anxiety.

Animals↗
PubMed2005

Short- and long-term memory are differentialy modulated by hippocampal nerve growth factor and fibroblast growth factor.

Rats were implanted with cannulae in the CA1 area of the dorsal hippocampus and trained in one-trial step-down inhibitory avoidance. Two retention tests were carried out in each animal, one at 1.5 h to measure short-term memory (STM) and another at 24 h to measure long-term memory (LTM). The purpose of the present study was to evaluate the modulation on hippocampal nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) on short- and long-term memory. Immediately after training, animals received 5 microl of NGF (0.05, 0.5 or 5.0 ng), bFGF (1.25, 12.5 or 125 ng) or saline per side. At the higher dose, NGF blocked STM. In contrast, NGF at dose of 0.5 and 5.0 ng improved LTM. The bFGF infusion at a dose of 125 ng enhanced LTM. However, bFGF did not alter STM. These findings indicate that hippocampal NGF and bFGF modulate STM and LTM in a different manner.

Animals↗
PubMed2005

Cognitive impairment in sepsis survivors from cecal ligation and perforation.

OBJECTIVE: Critical illness survivors present long-term cognitive impairment, including problems with memory and learning. We evaluated cognitive performance in rats that survived from sepsis induced by cecal ligation and puncture (CLP). DESIGN: Prospective, controlled experiment. SETTING: Animal basic science laboratory. SUBJECTS: Male Wistar rats, weighing 300-350 g. INTERVENTIONS: The rats underwent CLP (sepsis group) with "basic support" (saline at 50 mL/kg immediately and 12 hrs after CLP plus ceftriaxone at 30 mg/kg and clindamycin at 25 mg/kg 6, 12, and 18 hrs after CLP) or sham-operated (control group). MEASUREMENTS AND MAIN RESULTS: Ten days after surgery, the animals underwent three behavioral tasks: a) inhibitory avoidance task; b) habituation to an open field; and c) continuous multiple-trials step-down inhibitory avoidance task (CMSIA). In the habituation to an open-field task, there were no differences in the number of crossings and rearings. The sepsis group showed significantly decreased performance in latency retention compared with the sham group in inhibitory avoidance. Furthermore, when tested by the habituation to an open-field task, the sepsis group did not show any difference between training and test, indicating memory impairment. In the CMSIA, the sepsis group showed a significant increase in the number of training trials required to reach the acquisition criterion. CONCLUSION: Our data provide the first experimental demonstration that survivors from CLP show learning and memory impairment after complete physical recovery from sepsis.

Animals↗
PubMed2004

Haloperidol and clozapine, but not olanzapine, induces oxidative stress in rat brain.

Typical and atypical antipsychotic drugs have been shown to have different clinical and behavioral profiles. Haloperidol (HAL) is a typical neuroleptic that acts primarily as a D2 dopamine receptor antagonist. It has been proposed that reactive oxygen species play a causative role in neurotoxic effects induced by HAL. We evaluated oxidative damage in rat brain induced by chronic HAL, clozapine (CLO) or olanzapine (OLZ) administration. Adult male Wistar rats received daily injections of Hal (1.5mg/kg), CLO (25mg/kg) or OLZ (2.5, 5.0 or 10.0mg/kg). Control animals were given saline (SAL; NaCl 0.9%). Thiobarbituric acid reactive substances (TBARS) and protein carbonylation were measured in the hippocampus (HP), striatum (ST) and cortex (CX). TBARS was increased in the striatum after HAL treatment. In contrast, there was a decrease of TBARS levels induced by HAL, CLO and OLZ treatments in the cortex. Protein carbonyls after HAL and CLO treatment was increased in the hippocampus, compared to control. In hippocampus, OLZ did not show significant difference to control in both oxidative parameters. Our findings demonstrated that atypical antipsychotic CLO produced less oxidative damage than HAL and we did not find oxidative damage induced by OLZ.

Animals↗
PubMed2004

Treatment with N-acetylcysteine plus deferoxamine protects rats against oxidative stress and improves survival in sepsis.

OBJECTIVE: Oxidative stress plays an important role in the development of multiple organ failure and septic shock. Here we have evaluated the effects of a combination of antioxidants (N-acetylcysteine plus deferoxamine) in a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). DESIGN: Prospective, randomized, controlled experiment. SETTING: Animal basic science laboratory. SUBJECTS: Male Wistar rats, weighing 300-350 g. INTERVENTIONS: Rats subjected to CLP were treated with either N-acetylcysteine (20 mg/kg, 3 hrs, 6 hrs, 12 hrs, 18 hrs, and 24 hrs after CLP, subcutaneously) plus deferoxamine (20 mg/kg, 3 hrs and 24 hrs after CLP, subcutaneously) or vehicle with or without "basic support" (saline at 50 mL/kg immediately and 12 hrs after CLP plus ceftriaxone at 30 mg/kg and clindamycin 25 mg/kg every 6 hrs). MEASUREMENTS AND MAIN RESULTS: After 12 hrs, tissue myeloperoxidase (indicator of neutrophil infiltration), thiobarbituric acid reactive species (as a marker of oxidative stress), catalase and superoxide dismutase activities (antioxidant enzymes), and mitochondrial superoxide production (index of uncoupling of electron transfer chain) were measured in major organs involved in septic response. Rats treated with antioxidants had significantly lower myeloperoxidase activity and thiobarbituric acid reactive species formation in all organs studied. Mitochondrial superoxide production was significantly reduced by antioxidant treatment. Furthermore, antioxidants significantly improved the balance between catalase and superoxide dismutase activities. Survival in untreated septic rats was 10%. Survival increased to 40% with fluids and antibiotics. In rats treated only with N-acetylcysteine plus deferoxamine, survival was also significantly improved (47%) in a manner similar to basic support. Survival increased to 66% with basic support with N-acetylcysteine plus deferoxamine. CONCLUSIONS: Our data provide the first experimental demonstration that N-acetylcysteine plus deferoxamine reduces the consequences of septic shock induced by CLP in the rat, by decreasing oxidative stress and limiting neutrophil infiltration and mitochondrial dysfunction, thereby improving survival.

Acetylcysteine↗
PubMed2004

Protective effect of N-acetylcysteine and deferoxamine on carbon tetrachloride-induced acute hepatic failure in rats.

OBJECTIVE: Carbon tetrachloride (CCl4) is a lipid-soluble potent hepatotoxic; thus, it widely is used as an animal model of severe hepatic failure. Treatment with antioxidants may modulate the toxic effects of CCl4 on liver, generally with drug administration before CCl4, which can restrict its use in the clinical setting. We here describe the effects of N-acetylcysteine, deferoxamine, or both in the treatment of CCl4-induced hepatic failure. DESIGN: Prospective, randomized, controlled experiment. SETTING: Animal basic science laboratory. SUBJECTS: Male Wistar rats, weighing 200-250 g. INTERVENTIONS: Rats exposed to CCl4 were treated with N-acetylcysteine and/or deferoxamine or vehicle. MEASUREMENTS AND MAIN RESULTS: N-acetylcysteine plus deferoxamine treatment significantly attenuated hepatic and central nervous system oxidative damage after acute hepatic failure induced by CCl4. In addition, the serum levels of alanine aminotransferase, total bilirubin, and prothrombin time in the N-acetylcysteine plus deferoxamine group were significantly lower than those in the N-acetylcysteine or deferoxamine and saline groups. After N-acetylcysteine plus deferoxamine treatment, hepatocellular necrosis and inflammatory infiltration induced by carbon tetrachloride were greatly decreased. Survival in untreated rats was 5%. Survival increased to 25% and 35%, respectively, with N-acetylcysteine and deferoxamine treatment. In rats treated with N-acetylcysteine plus deferoxamine, survival was 80%. CONCLUSIONS: Our data provide the first experimental demonstration that N-acetylcysteine plus deferoxamine reduces mortality rate, decreases oxidative stress, and limits inflammatory infiltration and hepatocyte necrosis induced by CCl4 in the rat.

Acetylcysteine↗