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1.
Acta Psychiatr Scand ; 132(3): 211-7, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25891376

ABSTRACT

OBJECTIVE: Immune activation in bipolar disorder (BD) has been frequently reported. Damage-associated molecular patterns (DAMPs) are key players in the immune activation reaction. The aim of this study was to assess DAMP levels in drug-free patients with BD during acute episodes. METHOD: Serum levels of a predetermined set of DAMPs were assessed in drug-free patients with BD (n = 20) during an acute mood episode. We also included two control groups: healthy subjects, used as a negative control (n = 20); and patients with sepsis, used as a positive control for severe immune activation (n = 20). RESULTS: Multivariate analysis using generalized linear mixed model indicated that all DAMPs differed as a function of group membership after controlling for age and addressing multiplicity (P < 0.0006 for all comparisons). Follow-up analyses showed higher levels in BD subjects of circulating cell-free (ccf) nuclear (n)DNA (P = 0.02), HSP70 (P = 0.03) and HSP90α (P = 0.02) as compared to healthy subjects. Also, patients with BD showed lower levels of ccf nDNA (P = 0.04), HSP60 (P = 0.03), HSP70 (P = 0.01), and HSP90α (P = 0.002) as compared to patients with sepsis and higher levels of ccf mitochondrial DNA (P < 0.0001). CONCLUSION: The present findings may be linked to the inflammatory activity previously described among patients with BD and may help in the development of more targeted and personalized treatments for patients under acute episodes of BD.


Subject(s)
Bipolar Disorder/immunology , DNA/blood , Adult , Aged , Biomarkers/blood , Bipolar Disorder/blood , Bipolar Disorder/genetics , Case-Control Studies , Chaperonin 60/blood , DNA/genetics , Female , HSP70 Heat-Shock Proteins/blood , HSP90 Heat-Shock Proteins/blood , Humans , Male , Middle Aged , Multivariate Analysis , Precision Medicine
2.
Res Vet Sci ; 95(3): 1134-41, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24012348

ABSTRACT

In order to improve the understanding of the toxicity of pentavalent antimony (Sb(V)), we investigated the acute effects of meglumine antimoniate (MA) on the oxidative stress in heart, liver, kidney, spleen and brain tissue of mice. Levels of lipoperoxidation and protein carbonylation were measured to evaluate the oxidative status, whereas superoxide dismutase/catalase activity and glutathione levels were recorded to examine the antioxidative status. We observed that MA caused significant protein carbonylation in the heart, spleen and brain tissue. Increased lipoperoxidation was found in the liver and brain tissue. An imbalance between superoxide dismutase and catalase activities could be observed in heart, liver, spleen and brain tissue. Our results suggest that MA causes oxidative stress in several vital organs of mice. This indicates that the production of highly reactive oxygen and nitrogen species induced by MA might be involved in some of its toxic adverse effects.


Subject(s)
Antiprotozoal Agents/pharmacology , Meglumine/pharmacology , Organometallic Compounds/pharmacology , Oxidative Stress/drug effects , Animals , Antiprotozoal Agents/adverse effects , Brain/drug effects , Brain Chemistry/drug effects , Catalase/metabolism , Glutathione/analysis , Heart/drug effects , Kidney/chemistry , Kidney/drug effects , Lipid Peroxidation/drug effects , Liver/chemistry , Liver/drug effects , Meglumine/adverse effects , Meglumine Antimoniate , Mice , Myocardium/chemistry , Organometallic Compounds/adverse effects , Protein Carbonylation/drug effects , Spleen/chemistry , Spleen/drug effects , Superoxide Dismutase/metabolism
3.
Free Radic Res ; 47(3): 233-40, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23297832

ABSTRACT

Tissue methylmalonic acid (MMA) accumulation is the biochemical hallmark of methylmalonic acidemia. The disease is clinically characterized by progressive neurological deterioration and kidney failure, whose pathophysiology is still unclear. In the present work we investigated the effects of acute MMA administration on various parameters of oxidative stress in cerebral cortex and kidney of young rats, as well as the influence of acute renal failure on MMA-elicited effects on these parameters. Acute renal failure was induced by gentamicin, an aminoglycoside antibiotic whose utilization over prolonged periods causes nephrotoxicity. The administration of gentamicin alone increased carbonyl content and inhibited superoxide dismutase (SOD) activity in cerebral cortex, as well as increased thiobarbituric acid-reactive substances (TBA-RS) and sulfhydryl levels and diminished glutathione peroxidase activity in kidney. On the other hand, MMA administration increased TBA-RS levels in cerebral cortex and decreased SOD activity in kidney. Furthermore, the simultaneous administration of MMA and gentamicin to the rats provoked an augment in TBA-RS levels and superoxide generation in cerebral cortex and in TBA-RS, carbonyl and sulfhydryl levels in kidney, while diminished SOD activity in both studied tissues. Finally, nitrate/nitrite content, reduced glutathione levels, 2',7'-dihydrodichlorofluorescein oxidation and catalase activity were not affected by this animal treatment in either tissue. In conclusion, our present data are in line with the hypothesis that MMA acts as a toxin in brain and kidney of rats and suggest that renal injury potentiates the toxicity of MMA on oxidative stress parameters in brain and peripheral tissues.


Subject(s)
Acute Kidney Injury/metabolism , Amino Acid Metabolism, Inborn Errors/metabolism , Cerebral Cortex/metabolism , Kidney/metabolism , Oxidative Stress , Acute Kidney Injury/chemically induced , Amino Acid Metabolism, Inborn Errors/chemically induced , Animals , Catalase/metabolism , Creatinine/blood , Gentamicins , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Male , Methylmalonic Acid , Nitrates/metabolism , Nitrites/metabolism , Oxidation-Reduction , Protein Carbonylation , Rats , Rats, Wistar , Sulfhydryl Compounds/metabolism , Superoxide Dismutase/metabolism , Superoxides/metabolism , Thiobarbituric Acid Reactive Substances/metabolism
4.
Phlebology ; 28(8): 441-4, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23188814

ABSTRACT

OBJECTIVE: To assess the presence of pulmonary embolism and inflammation after polidocanol foam injection into the peripheral veins of rabbits. METHOD: The animals were treated with polidocanol foam (1 or 3 mg/kg) or vehicle. Early (15 minutes) and late (30 days) animals were evaluated by perfusional lung scintigraphy and histopathological examination. RESULTS: In the control group no alterations were found. After polidocanol foam injection it was observed that an important reduction of pulmonary perfusion in the early periods, was mainly in the left lung (P < 0.001), with consequent embolism in the histological evaluation. In late periods it was observed that the presence of thrombus was with fibrin in small veins, compatible with chronic thrombus and the presence of chronic pulmonary inflammation. CONCLUSIONS: The injection of polidocanol foam in experimental animals can induce venous embolism and chronic inflammatory infiltration.


Subject(s)
Lung/blood supply , Lung/pathology , Polyethylene Glycols/adverse effects , Pulmonary Embolism/chemically induced , Pulmonary Embolism/pathology , Sclerosing Solutions/adverse effects , Acute Disease , Animals , Chronic Disease , Female , Male , Polidocanol , Polyethylene Glycols/pharmacology , Rabbits , Sclerosing Solutions/pharmacology , Time Factors
5.
Eur J Clin Microbiol Infect Dis ; 31(8): 2005-9, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22302624

ABSTRACT

Pneumococcal meningitis is a severe infectious illness of the central nervous system (CNS), with high rates of lethality and morbidity, being that the microorganism and the host's inflammatory response are responsible for cerebral complications. Moreover, the blood­brain barrier (BBB) itself secretes cytokines and, because of the bipolar nature of the BBB, these substances can be secreted into either the CNS compartment or in the blood, so patients with acute bacterial meningitis frequently develop sepsis. Therefore, the aim of this study was to evaluate the cytokine/chemokine levels in different vessels and the BBB integrity after pneumococcal meningitis induction. Wistar rats were infected with Streptococcus pneumoniae, and the BBB integrity was investigated using Evan's blue dye. Also, blood from the carotid artery and jugular vein was collected in order to perform tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), interleukin-6 (IL-60 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) analyses by enzyme-linked immunosorbent assay (ELISA). CINC-1 levels were increased at 6 h in the arterial plasma and at 3 and 6 h in the jugular plasma. We observed BBB breakdown between 12 and 24 h in the hippocampus and at 12 and 18 h in the cortex after pneumococcal meningitis induction. The increase of CINC-1 occurred prior to the BBB breakdown. CINC-1 is a neutrophil chemoattractant and it may be related to early events in the pneumococcal meningitis pathophysiology.


Subject(s)
Blood-Brain Barrier/pathology , Chemokine CXCL1/blood , Meningitis, Pneumococcal/pathology , Animals , Blood Chemical Analysis , Enzyme-Linked Immunosorbent Assay , Male , Rats , Rats, Wistar , Time Factors
6.
Ecotoxicology ; 19(7): 1193-200, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20535553

ABSTRACT

Coal mining and incineration of solid residues of health services (SRHS) generate several contaminants that are delivered into the environment, such as heavy metals and dioxins. These xenobiotics can lead to oxidative stress overgeneration in organisms and cause different kinds of pathologies, including cancer. In the present study the concentrations of heavy metals such as lead, copper, iron, manganese and zinc in the urine, as well as several enzymatic and non-enzymatic biomarkers of oxidative stress in the blood (contents of lipoperoxidation = TBARS, protein carbonyls = PC, protein thiols = PT, α-tocopherol = AT, reduced glutathione = GSH, and the activities of glutathione S-transferase = GST, glutathione reductase = GR, glutathione peroxidase = GPx, catalase = CAT and superoxide dismutase = SOD), in the blood of six different groups (n = 20 each) of subjects exposed to airborne contamination related to coal mining as well as incineration of solid residues of health services (SRHS) after vitamin E (800 mg/day) and vitamin C (500 mg/day) supplementation during 6 months, which were compared to the situation before the antioxidant intervention (Ávila et al., Ecotoxicology 18:1150-1157, 2009; Possamai et al., Ecotoxicology 18:1158-1164, 2009). Except for the decreased manganese contents, heavy metal concentrations were elevated in all groups exposed to both sources of airborne contamination when compared to controls. TBARS and PC concentrations, which were elevated before the antioxidant intervention decreased after the antioxidant supplementation. Similarly, the contents of PC, AT and GSH, which were decreased before the antioxidant intervention, reached values near those found in controls, GPx activity was reestablished in underground miners, and SOD, CAT and GST activities were reestablished in all groups. The results showed that the oxidative stress condition detected previously to the antioxidant supplementation in both directly and indirectly subjects exposed to the airborne contamination from coal dusts and SRHS incineration, was attenuated after the antioxidant intervention.


Subject(s)
Air Pollutants, Occupational/toxicity , Antioxidants/therapeutic use , Coal Mining , Dietary Supplements , Oxidative Stress , Ascorbic Acid/administration & dosage , Ascorbic Acid/therapeutic use , Biomarkers/blood , Case-Control Studies , Environmental Exposure , Glutathione/blood , Glutathione/toxicity , Glutathione Reductase/blood , Glutathione Reductase/toxicity , Humans , Incineration , Lipid Peroxidation , Metals, Heavy/toxicity , Metals, Heavy/urine , Protein Carbonylation , Superoxide Dismutase/blood , Superoxide Dismutase/toxicity , Thiobarbituric Acid Reactive Substances/toxicity , Vitamin E/administration & dosage , Vitamin E/therapeutic use , alpha-Tocopherol/blood , alpha-Tocopherol/toxicity
8.
Peptides ; 30(10): 1914-20, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19616051

ABSTRACT

Neuropeptide S (NPS) and its receptor NPSR comprise a recently deorphaned G-protein-coupled receptor system. There is a body of evidence suggesting the involvement of NPS in wakefulness, anxiety, locomotor activity and oxidative stress damage. Considering that mood stabilizers block the stimulatory effect of psychostimulants in rodents, the present study aimed to investigate the effects of the pretreatment with lithium and valproate on the hyperlocomotion evoked by NPS. Another relevant action induced by lithium and valproate is the neuroprotection against oxidative stress. Thus, aiming to get further information about the mechanisms of action of NPS, herein we evaluated the effects of NPS, lithium and valproate, and the combination of them on oxidative stress damage. Behavioral studies revealed that the pretreatment with lithium (100 mg/kg, i.p.) and valproate (200 mg/kg, i.p.) prevented hyperlocomotion evoked by NPS 0.1 nmol. Importantly, the dose of valproate used in this study reduced mouse locomotion, although it did not reach the statistical significance. Biochemical analyses showed that lithium attenuated thiobarbituric reactive species (TBARS) formation in the striatum, cerebellum and hippocampus. NPS per se reduced TBARS levels only in the hippocampus. Valproate did not significantly affect TBARS levels in the brain. However, the combination of mood stabilizers and NPS blocked, instead of potentiate, the neuroprotective effects of each one. No relevant alterations were observed in carbonylated proteins after all treatments. Altogether, the present findings suggested that mainly the mood stabilizer lithium evoked antagonistic effects on the mediation of hyperlocomotion and protection against lipid peroxidation induced by NPS.


Subject(s)
Antipsychotic Agents , Behavior, Animal/drug effects , Lithium Compounds , Neuropeptides/metabolism , Animals , Anticonvulsants/metabolism , Anticonvulsants/pharmacology , Antipsychotic Agents/metabolism , Antipsychotic Agents/pharmacology , Humans , Lithium Compounds/metabolism , Lithium Compounds/pharmacology , Male , Mice , Motor Activity/drug effects , Receptors, G-Protein-Coupled , Thiobarbituric Acid Reactive Substances/metabolism , Valproic Acid/metabolism , Valproic Acid/pharmacology
9.
Chem Biol Interact ; 180(3): 478-84, 2009 Aug 14.
Article in English | MEDLINE | ID: mdl-19397901

ABSTRACT

Glycolaldehyde (GA) is a highly reactive aldehyde that can be generated during inflammation and hyperglycemia. It can react with arginine and lysine residues impairing protein function. As inflammation and diabetes present haemostatic dysfunction, we hypothesized that GA could participate in this process. The aim of this study was to investigate if plasma incubated in the presence of GA presents alteration in the coagulation process. We also aimed to evaluate the role of fibrinogen in GA-induced haemostatic dysfunction. For this purpose, plasma and fibrinogen were each incubated separately, either in the presence or absence of 1 mM GA for 8 and 4 h, respectively. After that, plasma coagulation and fibrin polymerization kinetics were recorded, as well as the kinetic of plasma clot digestion and fibrinolysis protein carbonylation was quantified. An SDS-PAGE was run to check the presence of cross-linking between fibrinogen chains. GA induced a delay in plasma coagulation and in fibrin polymerization. Maximum absorbance decreased after GA treatment, indicating the generation of thinner fibers. Fibrin generated after complete coagulation showed resistance to enzymatic digestion, which could be related to the generation of thinner fibers. Protein carbonylation also increased after GA treatment. All parameters could be reversed with AMG (a carbonyl trap) co-treatment. The data presented herein indicate that GA causes post-translational modification of lysine and arginine residues, which are central to many events involving fibrinogen to fibrin conversion, as well as to fibrinolysis. These modifications lead to the generation of persistent clots and may contribute to mortality seen in pathologies such diabetes and sepsis.


Subject(s)
Acetaldehyde/analogs & derivatives , Blood Coagulation/drug effects , Fibrinogen/chemistry , Trypsin/chemistry , Acetaldehyde/chemistry , Acetaldehyde/pharmacology , Fibrinogen/metabolism , Fibrinolysis , Kinetics , Protein Carbonylation/drug effects , Protein Processing, Post-Translational , Trypsin/metabolism
10.
Inflamm Res ; 58(2): 89-93, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19184359

ABSTRACT

BACKGROUND: It seems that a balance between anti and pro-inflammatory responses must be kept to eliminate the pathogen without inducing inflammatory damage in the host. Thus we determined the relation between macrophage activation and the severity and clinical outcome in septic patients. MATERIAL AND METHODS: This was a prospective study at a tertiary general intensive care unit. Thirty-three patients admitted with sepsis, severe sepsis or septic shock were included. As a control group, healthy volunteers were included matched to septic patients by age and sex. Peritoneal rat macrophages were cultured with 2% serum from healthy volunteers or from septic patients for determination of phagocytic potential or the capacity to produce cytokines. RESULTS: TNF and IL1 secretion by macrophages activated with serum from sepsis and severe sepsis patients was higher than with serum from healthy controls. In addition, proinflammatory cytokines released in vitro from macrophages, but not determined directly in the serum from patients, were lower in non-survivor septic patients when compared to survivors. In contrast, IL-10 secretion by macrophages activated with serum from septic patients was higher in nonsurvivors. In the septic shock group we observed a diminution in the phagocytic index compared to sepsis and severe sepsis groups, and the phagocytic index was higher in sepsis survivors. CONCLUSIONS: Markers of antiinflammation are predominant in more severe types of sepsis suggesting that antiinflammation is related to mortality.


Subject(s)
Macrophage Activation , Severity of Illness Index , Shock, Septic , Adult , Aged , Aged, 80 and over , Animals , Cells, Cultured , Cytokines/blood , Cytokines/immunology , Humans , Macrophages, Peritoneal/cytology , Macrophages, Peritoneal/immunology , Middle Aged , Nitric Oxide/metabolism , Phagocytosis , Prospective Studies , Rats , Rats, Wistar , Shock, Septic/blood , Shock, Septic/immunology , Treatment Outcome
11.
Pharmacol Biochem Behav ; 91(4): 636-42, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19022279

ABSTRACT

Neuropeptide S (NPS) is a recently discovered peptide which induces hyperlocomotion, anxiolysis and wakefulness. This study aimed to compare behavioral and biochemical effects of NPS with amphetamine (AMPH), and diazepam (DZP). To this aim, the effects of NPS (0.01, 0.1 and 1 nmol, ICV), AMPH (2 mg/kg, IP) and DZP (1 mg/kg, IP) on locomotion and oxidative stress parameters were assessed in mouse brain structures. The administration of NPS and AMPH, but not DZP, increased locomotion compared to control. Biochemical analyses revealed that AMPH increased carbonylated proteins in striatum, but did not alter lipid peroxidation. DZP increased lipid peroxidation in the cortex and cerebellum, and increased protein carbonyl formation in the striatum. In contrast, NPS reduced carbonylated protein in the cerebellum and striatum, and also lipid peroxidation in the cortex. Additionally, the treatment with AMPH increased superoxide dismutase (SOD) activity in the striatum, while it did not affect catalase (CAT) activity. DZP did not alter SOD and CAT activity. NPS inhibited the increase of SOD activity in the cortex and cerebellum, but little influenced CAT activity. Altogether, this is the first evidence of a putative role of NPS in oxidative stress and brain injury.


Subject(s)
Amphetamine/pharmacology , Brain Chemistry/drug effects , Central Nervous System Stimulants/pharmacology , Diazepam/pharmacology , Hypnotics and Sedatives/pharmacology , Motor Activity/drug effects , Neuropeptides/pharmacology , Oxidative Stress/drug effects , Animals , Catalase/metabolism , Injections, Intraperitoneal , Injections, Intraventricular , Lipid Peroxidation/drug effects , Male , Mice , Nerve Tissue Proteins/metabolism , Protein Carbonylation/drug effects , Superoxide Dismutase/metabolism
12.
Peptides ; 29(10): 1726-31, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18590783

ABSTRACT

OBJECTIVE: To determine the effects of RC-3095 in clinical and histopathologic parameters and inflammatory mediators on complete Freund's adjuvant-induced arthritis (CFA). METHODS: The arthritis was induced by injection of CFA into the left hind footpad. The animals were divided into control, vehicle injected control, placebo group (saline subcutaneously 50ml/kg, once daily for 8 days after modeling), treatment group (0.3mg/kg of RC-3095 subcutaneously, once daily for 8 days after induction). Clinical evaluation was accomplished daily, through scoring of the paw edema. The animals were sacrificed 15 days after induction for collection of hind foot joints for histology. We used a histological scoring system which was previously described, and interferon (INF)-gamma, interleukin (IL)-1beta, tumor necrosis factor (TNF), interleukin (IL)-6 and interleukin (IL)-10 were measured by ELISA. RESULTS: There was a significant inhibition of joint histological findings in the RC-3095 treated group, including synovial inflammatory infiltration and hyperplasia, cartilage and bone erosion. IFN-gamma, IL-1beta, TNF, IL-6 and IL-10 serum levels were significantly lower in the treated group. Paw swelling and subcutaneous inflammation, evaluated clinically, were not different between CFA-induced groups. CONCLUSIONS: RC-3095 was able to improve experimental arthritis, attenuate joint damage and decrease serum levels of IFN-gamma, IL-1beta, TNF, IL-6 and IL-10. These data indicate that interference with GRP pathway is a potential new strategy for the treatment of RA that needs further investigational studies.


Subject(s)
Arthritis, Experimental/drug therapy , Bombesin/analogs & derivatives , Peptide Fragments/therapeutic use , Receptors, Bombesin/antagonists & inhibitors , Animals , Arthritis, Experimental/immunology , Arthritis, Experimental/pathology , Bombesin/therapeutic use , Freund's Adjuvant/immunology , Interferon-gamma/blood , Interleukin-10/blood , Interleukin-1beta/blood , Interleukin-6/blood , Male , Placebos , Random Allocation , Rats , Rats, Wistar , Tarsus, Animal/immunology , Tarsus, Animal/pathology , Tumor Necrosis Factor-alpha/blood
14.
Braz J Med Biol Res ; 40(6): 831-7, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17581683

ABSTRACT

Sepsis and its complications are the leading causes of mortality in intensive care units, accounting for 10-50% of deaths. Intensive care unit survivors present long-term cognitive impairment, including alterations in memory, attention, concentration, and/or global loss of cognitive function. In the present study, we investigated behavioral alterations in sepsis-surviving rats. One hundred and ten male Wistar rats (3-4 months, 250-300 g) were submitted to cecal ligation and puncture (CLP), and 44 were submitted to sham operation. Forty-four rats (40%) survived after CLP, and all sham-operated animals survived and were used as control. Twenty animals of each group were used in the object recognition task (10 in short-term memory and 10 in long-term memory), 12 in the plus-maze test and 12 in the forced swimming test. Ten days after surgery, the animals were submitted individually to an object recognition task, plus-maze and forced swimming tests. A significant impairment of short- and long-term recognition memory was observed in the sepsis group (recognition index 0.75 vs 0.55 and 0.74 vs 0.51 for short- and long-term memory, respectively (P < 0.05). In the elevated plus-maze test no difference was observed between groups in any of the parameters assessed. In addition, sepsis survivors presented an increase in immobility time in the forced swimming test (180 vs 233 s, P < 0.05), suggesting the presence of depressive-like symptoms in these animals after recovery from sepsis. The present results demonstrated that rats surviving exposure to CLP, a classical sepsis model, presented recognition memory impairment and depressive-like symptoms but not anxiety-like behavior.


Subject(s)
Anxiety Disorders/etiology , Avoidance Learning/physiology , Cecal Diseases/physiopathology , Depressive Disorder/etiology , Intestinal Obstruction/physiopathology , Intestinal Perforation/physiopathology , Shock, Septic/physiopathology , Animals , Anxiety Disorders/physiopathology , Depressive Disorder/physiopathology , Disease Models, Animal , Male , Maze Learning , Memory, Short-Term/physiology , Rats , Rats, Wistar , Shock, Septic/psychology , Swimming
15.
Braz. j. med. biol. res ; 40(6): 831-837, June 2007. graf
Article in English | LILACS | ID: lil-452677

ABSTRACT

Sepsis and its complications are the leading causes of mortality in intensive care units, accounting for 10-50 percent of deaths. Intensive care unit survivors present long-term cognitive impairment, including alterations in memory, attention, concentration, and/or global loss of cognitive function. In the present study, we investigated behavioral alterations in sepsis-surviving rats. One hundred and ten male Wistar rats (3-4 months, 250-300 g) were submitted to cecal ligation and puncture (CLP), and 44 were submitted to sham operation. Forty-four rats (40 percent) survived after CLP, and all sham-operated animals survived and were used as control. Twenty animals of each group were used in the object recognition task (10 in short-term memory and 10 in long-term memory), 12 in the plus-maze test and 12 in the forced swimming test. Ten days after surgery, the animals were submitted individually to an object recognition task, plus-maze and forced swimming tests. A significant impairment of short- and long-term recognition memory was observed in the sepsis group (recognition index 0.75 vs 0.55 and 0.74 vs 0.51 for short- and long-term memory, respectively (P < 0.05). In the elevated plus-maze test no difference was observed between groups in any of the parameters assessed. In addition, sepsis survivors presented an increase in immobility time in the forced swimming test (180 vs 233 s, P < 0.05), suggesting the presence of depressive-like symptoms in these animals after recovery from sepsis. The present results demonstrated that rats surviving exposure to CLP, a classical sepsis model, presented recognition memory impairment and depressive-like symptoms but not anxiety-like behavior.


Subject(s)
Animals , Male , Rats , Anxiety Disorders/etiology , Avoidance Learning/physiology , Cecal Diseases/physiopathology , Depressive Disorder/etiology , Intestinal Obstruction/physiopathology , Intestinal Perforation/physiopathology , Shock, Septic/physiopathology , Anxiety Disorders/physiopathology , Disease Models, Animal , Depressive Disorder/physiopathology , Maze Learning , Memory, Short-Term/physiology , Rats, Wistar , Swimming , Shock, Septic/psychology
16.
Respir Med ; 101(8): 1830-5, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17376663

ABSTRACT

Pulmonary rehabilitation (PR) improves physical capacity and health quality in patients with chronic obstructive pulmonary disease (COPD). However, the effect of exercise on oxidative stress markers in COPD patients is only partially known. This study was designed to evaluate the oxidative stress response to long-term exercise in patients with COPD enrolled in a PR program. Fifteen COPD patients (FEV1 < 60%), age between 50 and 60 years, ex-smokers, were separated in two groups: exercise-trained (n=8) and sedentary group (n=7). Exercise consisted of an 8-week conditioning program using a cycle ergometer (three times a week, 1h session). An endurance test (60% of maximal load in an incremental cycle test) was performed before and after PR. Blood samples were obtained at baseline and immediately after each endurance test. We measured the index of lipid peroxidation, thiobarbituric acid reactive species (TBARS), total radical-trapping antioxidant parameter (TRAP) and xanthine oxidase (XO) activity. TRAP was significantly different between the exercise-trained group and sedentary group of COPD patients. Baseline TBARS values were increased after the exercise training program but decreased after the endurance test. XO decrease after effort in the trained and untrained groups. The results suggest that patients with COPD are characterized by increased systemic and pulmonary oxidative stress markers both at rest as well as induced by cardiopulmonary exercise test and that PR program was associated with decreased systemic exercise-induced oxidative damage.


Subject(s)
Exercise Therapy , Oxidative Stress , Pulmonary Disease, Chronic Obstructive/rehabilitation , Breath Tests , Humans , Middle Aged , Pulmonary Disease, Chronic Obstructive/metabolism , Respiratory Function Tests
17.
Food Chem Toxicol ; 45(4): 656-61, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17169472

ABSTRACT

The leaf extract of Passiflora alata Dryander (P. alata) has been demonstrated to possess antioxidant activity in vitro. The aim of this study was to investigate the effects of P. alata leaf extract pretreatment on carbon tetrachloride-treated rats. Male Wistar rats were randomly allocated into four groups: group 1 (control - vehicle), group 2 and 3 (P. alata extract - 1 and 5mg/kg, respectively) and group 4 (trolox - 0.18mg/kg). Rats received daily pretreatment by oral gavage for 30 days followed by a single dose of CCl(4) (3ml/kg i.p. in vegetable oil) on the 30th day and were killed after 6h. The pretreatment with the P. alata extract provided significant protection to liver, evidenced by lower degree of necrosis, decreased lipid peroxidation (TBARS) and higher catalase and superoxide dismutase activities. Additionally, pretreated-rats with P. alata (5mg/kg) showed significantly decreased cardiac TBARS levels. Our results indicate that a low oral dose of P. alata leaf extract has both hepato and cardioprotective effects on rats treated with CCl(4).


Subject(s)
Passiflora , Plant Extracts/pharmacology , Animals , Carbon Tetrachloride/toxicity , Liver/drug effects , Liver/metabolism , Liver/pathology , Male , Oxidation-Reduction , Rats , Rats, Wistar
18.
Environ Toxicol Pharmacol ; 23(2): 198-204, 2007 Mar.
Article in English | MEDLINE | ID: mdl-21783758

ABSTRACT

Malathion is an insecticide of the group of organophosphate pesticides (OPs), which shows strong insecticidal effects. However, it possesses mutagenic and carcinogenic properties and shows organ-specific toxicity in relation to the heart, kidney and other vertebrate organs. The exact mechanism of the genotoxic effects of malathion is not yet known. Free radical damage is an important direct or indirect factor in several pathological and toxicological processes, including malathion poisoning. The aim of the present study was the evaluation of oxidative damage in different tissues of Wistar rats, administered intra peritoneally at doses of 25, 50, 100 and 150mgmalathion/kg, after acute and sub-chronic malathion exposure. Oxidative stress evaluation was based on lipid peroxidation by levels of thiobarbituric acid reactive substances (TBARS), protein oxidation by levels of carbonyl groups, and also on the activities of superoxide dismutase and catalase, two antioxidant enzymes that detoxity superoxide radical (O(2)(-)) and hydrogen peroxide, respectively. The results showed that the most sensitive targets of oxidative damage were kidney, lung and diaphragm after acute treatment, and liver, quadriceps and serum after sub-chronic treatment. Also, in general, increased lipid peroxidation measured as TBARS levels seems to be a better biomarker of oxidative stress compared to the contents of protein carbonyls after acute and sub-chronic malathion treatments. The present findings reinforce the concept that oxidative stress and particularly lipoperoxidation, are involved in OPs toxicity.

19.
Neuropharmacology ; 51(2): 350-7, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16735043

ABSTRACT

Although the gastrin-releasing peptide-preferring bombesin receptor (GRPR) has been implicated in memory formation, the underlying molecular events are poorly understood. In the present study, we examined interactions between the GRPR and cellular signaling pathways in influencing memory consolidation in the hippocampus. Male Wistar rats received bilateral infusions of bombesin (BB) into the dorsal hippocampus immediately after inhibitory avoidance (IA) training. Intermediate doses of BB enhanced, whereas a higher dose impaired, 24-h IA memory retention. The BB-induced memory enhancement was prevented by pretraining infusions of a GRPR antagonist or inhibitors of protein kinase C (PKC), mitogen-activated protein kinase (MAPK) kinase and protein kinase A (PKA), but not by a neuromedin B receptor (NMBR) antagonist. We next further investigated the interactions between the GRPR and the PKA pathway. BB-induced enhancement of consolidation was potentiated by coinfusion of activators of the dopamine D1/D5 receptor (D1R)/cAMP/PKA pathway and prevented by a PKA inhibitor. We conclude that memory modulation by hippocampal GRPRs is mediated by the PKC, MAPK, and PKA pathways. Furthermore, pretraining infusion of BB prevented beta-amyloid peptide (25-35)-induced memory impairment, supporting the view that the GRPR is a target for the development of cognitive enhancers for dementia.


Subject(s)
Hippocampus/physiology , Memory , Receptors, Bombesin/physiology , Amyloid beta-Peptides/pharmacology , Animals , Bombesin/pharmacology , Cyclic AMP/physiology , Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , Cyclic AMP-Dependent Protein Kinases/physiology , Hippocampus/drug effects , Male , Mitogen-Activated Protein Kinase Kinases/physiology , Peptide Fragments/pharmacology , Protein Kinase C/physiology , Rats , Rats, Wistar , Receptors, Bombesin/agonists , Receptors, Dopamine D5/agonists , Signal Transduction
20.
Liver Int ; 26(4): 477-85, 2006 May.
Article in English | MEDLINE | ID: mdl-16629652

ABSTRACT

BACKGROUND/AIMS: Oxidative stress plays an important role in liver fibrosis. Under pathological conditions, hepatic stellate cells (HSC) undergo an activation process, developing a myofibroblast-like phenotype from the lipocyte phenotype. In this study, we determined the levels of oxidative stress and proliferation in different activation states of an experimental model of mouse HSC, the GRX cell line. These cells can be induced in vitro to display a more activated state or a quiescent phenotype. METHODS/RESULTS: We observed increased oxidative damage and higher levels of reactive oxygen species, measured by thiobarbituric acid reactive species and 2',7'-dichlorofluorescein diacetate, respectively, and diminished catalase activity in activated cells. Activation decreased proliferation and increased the number of cells in G2/M. Antioxidants N-acetylcysteine and Trolox varied in their capacity to correct the oxidative stress and proliferation status. CONCLUSIONS: The differences in physiological functions of stellate cell phenotypes suggest a relationship between oxidative stress levels and activation state.


Subject(s)
Liver Cirrhosis/physiopathology , Liver/cytology , Liver/physiology , Oxidative Stress/physiology , Acetylcysteine/pharmacology , Animals , Antioxidants/pharmacology , Catalase/metabolism , Cell Line , Cell Proliferation/drug effects , Chromans/pharmacology , Cytokines/pharmacology , Liver/drug effects , Liver Cirrhosis/pathology , Mice , Oxidative Stress/drug effects , Phenotype , Reactive Oxygen Species/metabolism , Tumor Necrosis Factor-alpha/pharmacology , Vitamin E/pharmacology
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