31 results on '"Leffa DD"'
Search Results
2. Hibiscus acetosella extract protects against alkylating agent-induced DNA damage in mice.
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Vilela TC, Leffa DD, Damiani AP, Damazio DDC, Manenti AV, Carvalho TJG, Ramlov F, Amaral PA, and Andrade VM
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- Animals, Chromatography, High Pressure Liquid, DNA Damage genetics, Male, Methyl Methanesulfonate, Mice, Mutagens, Plant Extracts administration & dosage, Alkylating Agents pharmacology, Antimutagenic Agents pharmacology, DNA Damage drug effects, Hibiscus chemistry, Plant Extracts pharmacology, Plant Leaves chemistry, Protective Agents pharmacology
- Abstract
Hibiscus acetosella was shown to exert beneficial effects in humans and animal models however, the effects of this plant on DNA are unknown. The aim of this study was to determine the antigenotoxic and antimutagenic effects of H. acetosella extracts on alkylating agent methyl methanesulfonate (MMS) in vivo in mice. Initially, we performed analysis of phenolic compounds in extracts of H. acetosella by high-performance liquid chromatography (HPLC). Next, mice were divided into 8 groups and treated with distilled water or plant extract (0.1 ml/10 g) by gavage for 15 days, followed by intraperitoneal (ip) administration of saline solution or MMS (40 mg/Kg b.w) on day 16. Caffeic acid, following by gallic acid, gallocatechin, coumaric acid, and 3,4-dihydroxybenzoic acid were found to be present in extracts of H. acetosella leaves. In peripheral blood analysis of groups receiving pretreatment with H. acetosella at doses of 50 or 100 mg/kg plus MMS decreased DNA damage as evidenced by comet assay and Micronucleus assays relative to MMS alone. These results suggested that H. acetosella extracts exerted protective effects dose dependent against genotoxicity and mutagenicity induced by alkylating agents.
- Published
- 2018
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3. Effects of Acerola (Malpighia emarginata DC.) Juice Intake on Brain Energy Metabolism of Mice Fed a Cafeteria Diet.
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Leffa DD, Rezin GT, Daumann F, Longaretti LM, Dajori AL, Gomes LM, Silva MC, Streck EL, and de Andrade VM
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- Animals, Antioxidants administration & dosage, Ascorbic Acid administration & dosage, Brain drug effects, Dietary Supplements, Eating physiology, Energy Metabolism drug effects, Male, Mice, Obesity diet therapy, Obesity etiology, Obesity metabolism, Plant Extracts administration & dosage, Plant Extracts metabolism, Random Allocation, Brain metabolism, Diet, Western adverse effects, Energy Metabolism physiology, Fruit and Vegetable Juices, Malpighiaceae metabolism
- Abstract
Obesity is a multifactorial disease that comes from an imbalance between food intake and energy expenditure. Moreover, studies have shown a relationship between mitochondrial dysfunction and obesity. In the present study, we investigated the effect of acerola juices (unripe, ripe, and industrial) and its main pharmacologically active components (vitamin C and rutin) on the activity of enzymes of energy metabolism in the brain of mice fed a palatable cafeteria diet. Two groups of male Swiss mice were fed on a standard diet (STA) or a cafeteria diet (CAF) for 13 weeks. Afterwards, the CAF-fed animals were divided into six subgroups, each of which received a different supplement for one further month (water, unripe, ripe or industrial acerola juices, vitamin C, or rutin) by gavage. Our results demonstrated that CAF diet inhibited the activity of citrate synthase in the prefrontal cortex, hippocampus, and hypothalamus. Moreover, CAF diet decreased the complex I activity in the hypothalamus, complex II in the prefrontal cortex, complex II-III in the hypothalamus, and complex IV in the posterior cortex and striatum. The activity of succinate dehydrogenase and creatine kinase was not altered by the CAF diet. However, unripe acerola juice reversed the inhibition of the citrate synthase activity in the prefrontal cortex and hypothalamus. Ripe acerola juice reversed the inhibition of citrate synthase in the hypothalamus. The industrial acerola juice reversed the inhibition of complex I activity in the hypothalamus. The other changes were not reversed by any of the tested substances. In conclusion, we suggest that alterations in energy metabolism caused by obesity can be partially reversed by ripe, unripe, and industrial acerola juice.
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- 2017
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4. DNA damage after chronic oxytocin administration in rats: a safety yellow light?
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Leffa DD, Daumann F, Damiani AP, Afonso AC, Santos MA, Pedro TH, Souza RP, and Andrade VM
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- Animals, Body Weight drug effects, Male, Rats, Rats, Wistar, DNA Damage drug effects, Hippocampus drug effects, Oxytocin pharmacology
- Abstract
Adjuvant therapy is a common therapeutic strategy used for schizophrenia management. Oxytocin has shown promising results as antipsychotic adjuvant in patients with schizophrenia. Although short-term clinical studies have indicated tolerability and no major side-effect manifestation, long-term studies remain needed. In this study, we investigated whether oxytocin chronic administration in rats may lead to brain DNA damage by comet assay. Our results suggest that 21 and 56-day treatment with once daily intraperitoneal oxytocin (0.1, 1.0 and 10.0 mg/kg) may cause substantial DNA damage in hippocampus. We have not found differences on body weight gain. Our findings also point that further clinical and preclinical studies evaluating oxytocin safety after chronic exposure are necessary.
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- 2017
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5. Elemental composition of vegetables cultivated over coal-mining waste.
- Author
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Zocche JJ, Rohr P, Damiani AP, Leffa DD, Martins MC, Zocche CM, Teixeira KO, Borges GD, Jesus MM, Santos CEID, Dias JF, and Andrade VM
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- Animals, Mice, Soil Pollutants toxicity, Vegetables toxicity, Waste Disposal, Fluid, Coal Mining, Food Contamination analysis, Liver drug effects, Sewage chemistry, Soil Pollutants analysis, Vegetables chemistry
- Abstract
We assessed elemental composition of the liver in mice subjected to one-time or chronic consumption of the juice of vegetables cultivated in a vegetable garden built over deposits of coal waste. Lactuca sativa L. (lettuce), Beta vulgaris L. (beet), Brassica oleracea L. var. italica (broccoli) and Brassica oleracea L. var. acephala (kale) were collected from the coal-mining area and from a certified organic farm (control). Elemental composition was analyzed by particle-induced X-ray emission (PIXE) method. Concentrations of Mg, S, and Ca of mice subjected to one-time consumption of broccoli and concentrations of these same elements plus Si of mice receiving kale were higher in the coal-mining area. Concentrations of P, K, and Cu were increase after chronic consumption of lettuce from the coal-mining area, whereas the levels of Si, P, K, Fe, and Zn were higher in the group consuming kale from the coal-mining area. Our data suggests that people consuming vegetables grown over coal wastes may ingest significant amounts of chemical elements that pose a risk to health, since these plants contain both essential and toxic metals in a wide range of concentrations, which can do more harm than good.
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- 2017
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6. Effect of green juice and their bioactive compounds on genotoxicity induced by alkylating agents in mice.
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Fagundes GE, Damiani AP, Borges GD, Teixeira KO, Jesus MM, Daumann F, Ramlov F, Carvalho T, Leffa DD, Rohr P, and Moraes De Andrade V
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- Animals, Brassica chemistry, Chromatography, High Pressure Liquid, Comet Assay, Cyclophosphamide antagonists & inhibitors, Cyclophosphamide pharmacology, DNA Damage drug effects, Lutein analysis, Lutein pharmacology, Male, Methyl Methanesulfonate antagonists & inhibitors, Methyl Methanesulfonate pharmacology, Mice, Mutagens adverse effects, Mutagens analysis, beta Carotene analysis, beta Carotene pharmacology, Alkylating Agents adverse effects, Fruit and Vegetable Juices analysis
- Abstract
Kale juice (Brassica oleracea L. var. acephala D.C.) is a reliable source of dietary carotenoids and typically contains the highest concentrations of lutein (LT) and beta-carotene (BC) among green leafy vegetables. As a result of their antioxidant properties, dietary carotenoids are postulated to decrease the risk of disease occurrence, particularly certain cancers. The present study aimed to (1) examine the genotoxic and antigenotoxic activity of natural and commercially available juices derived from Brassica oleracea and (2) assess influence of LT or BC against DNA damage induced by alkylating agents such as methyl methanesulfonate (MS) or cyclophosphamide (CP) in vivo in mice. Male Swiss mice were divided into groups of 6 animals, which were treated with water, natural, or commercial Brassica oleraceae juices (kale), LT, BC, MMS, or CP. After treatment, DNA damage was determined in peripheral blood lymphocytes using the comet assay. Results demonstrated that none of the Brassica oleraceae juices or carotenoids produced genotoxic effects. In all examined cell types, kale juices or carotenoids inhibited DNA damage induced by MMS or CP administered either pre- or posttreatment by 50 and 20%, respectively. Under our experimental conditions, kale leaf juices alone exerted no marked genotoxic or clastogenic effects. However, a significant decrease in DNA damage induced by MMS or CP was noted. This effect was most pronounced in groups that received juices, rather than carotenoids, suggesting that the synergy among constituents present in the food matrix may be more beneficial than the action of single compounds. Data suggest that the antigenotoxic properties of kale juices may be of therapeutic importance.
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- 2017
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7. Anesthetic Ketamine-Induced DNA Damage in Different Cell Types In Vivo.
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Leffa DD, Bristot BN, Damiani AP, Borges GD, Daumann F, Zambon GM, Fagundes GE, and de Andrade VM
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- Animals, Blood Cells drug effects, Blood Cells metabolism, Comet Assay, Mice, Xylazine toxicity, Anesthetics toxicity, DNA Damage, Ketamine toxicity
- Abstract
The use of a combination of ketamine and xylazine is broadly used either for anesthesia or euthanasia in rodent animal models in research. However, the genotoxicity and mutagenic effects of these drugs are unknown. Therefore, the aim of this study was to evaluate these effects to help the understanding of elevated values in negative controls in genotoxic/mutagenic assays. Sixty CF-1 mice were divided into ten groups of six mice per group: negative control (saline), positive control (doxorubicin, 40 mg/kg), ketamine at 80 mg/kg and xylazine at 10 mg/kg, ketamine at 100 mg/kg and xylazine at 10 mg/kg, ketamine at 140 mg/kg and xylazine at 8 mg/kg, ketamine at 80 mg/kg, ketamine at 100 mg/kg, ketamine at 140 mg/kg, xylazine at 8 mg/kg, and xylazine at 10 mg/kg. After drug induction, the blood cells were analyzed at 1, 12, and 24 h by the comet assay, while the brain cortex, liver, and kidney cells were verified just at 24 h by the comet assay and bone marrow was tested at 24 h by micronucleus test. The positive control was significantly different in relation to the negative control in all times and tissue analyzed. The dose of ketamine at 140 mg/kg plus xylazine at 8 mg/kg and only ketamine at 140 mg/kg exhibited a genotoxic effect in blood and brain cells at all the times analyzed. The doses of ketamine at 80 and 100 mg/kg in association or not with xylazine showed increased DNA damage at 1 and 12 h, but this effect was reversed after 24 h of drug administration. The liver, kidney, and bone marrow cells of animals treated with ketamine or xylazine isolated or combined did not differ when compared with the negative control. Then, our findings emphasize the necessity of more studies that prove safety of the ketamine use, since that anesthetic can be able to induce false-negative results in genotoxic experimental studies.
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- 2016
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8. Diphenyl diselenide attenuates oxidative stress and inflammatory parameters in ulcerative colitis: A comparison with ebselen.
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Petronilho F, Michels M, Danielski LG, Goldim MP, Florentino D, Vieira A, Mendonça MG, Tournier M, Piacentini B, Giustina AD, Leffa DD, Pereira GW, Pereira VD, and Rocha JB
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- Animals, Azoles pharmacology, Benzene Derivatives pharmacology, Catalase metabolism, Colitis chemically induced, Colitis metabolism, Colon drug effects, Colon metabolism, Disease Models, Animal, Inflammation chemically induced, Inflammation metabolism, Isoindoles, Male, Neutrophils, Organoselenium Compounds pharmacology, Rats, Rats, Wistar, Reactive Oxygen Species metabolism, Superoxide Dismutase metabolism, Azoles therapeutic use, Benzene Derivatives therapeutic use, Colitis drug therapy, Inflammation drug therapy, Organoselenium Compounds therapeutic use, Oxidative Stress drug effects
- Abstract
Objetive: The aim of this study was to evaluate the effects of diphenyl diselenide (PhSe)2 and ebselen (EB) in ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in rats., Methods: The effects of (PhSe)2 and EB in rats submitted to DSS-induced colitis were determined by measurement of oxidative stress parameters, inflammatory response and bowel histopathological alterations., Results: Animals developed moderate to severe neutrophil infiltration in histopathology assay in DSS rats and (PhSe)2 improved this response. Moreover, the treatment with (PhSe)2 decreased the oxidative damage in lipids and proteins, as well as reversed the superoxide dismutase (SOD) and catalase (CAT) levels in rats treated with DSS. EB was able only to reverse damage in lipids and the low levels of SOD in this animal model., Conclusions: The organoselenium compounds tested demonstrated an anti-inflammatory and antioxidant activity reducing the colon damage, being (PhSe)2 more effective than EB., (Copyright © 2016 Elsevier GmbH. All rights reserved.)
- Published
- 2016
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9. Is bipolar disorder associated with accelerating aging? A meta-analysis of telomere length studies.
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Colpo GD, Leffa DD, Köhler CA, Kapczinski F, Quevedo J, and Carvalho AF
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- Adult, Case-Control Studies, Comorbidity, Female, Humans, Male, Middle Aged, Prevalence, Telomere genetics, Aging genetics, Bipolar Disorder genetics, Telomere metabolism, Telomere Homeostasis
- Abstract
Background: Bipolar disorder (BD) is associated with a reduced life expectancy compared to the general population mainly due to a high prevalence of comorbid somatic illnesses. A model of accelerated aging has been proposed as a potential explanation to these epidemiological findings. Nevertheless, studies measuring telomere length (TL) in patients with BD compared to healthy controls have provided mixed results., Objective: To compare TL between BD patients and healthy controls, and to search for potential modeP
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- 2015
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10. Effects of Supplemental Acerola Juice on the Mineral Concentrations in Liver and Kidney Tissue Samples of Mice Fed with Cafeteria Diet.
- Author
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Leffa DD, dos Santos CE, Daumann F, Longaretti LM, Amaral L, Dias JF, da Silva J, and Andrade VM
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- Analysis of Variance, Animals, Antioxidants administration & dosage, Antioxidants pharmacology, Ascorbic Acid administration & dosage, Ascorbic Acid pharmacology, Kidney drug effects, Liver drug effects, Male, Malpighiaceae chemistry, Mice, Rutin administration & dosage, Rutin pharmacology, Diet, Dietary Supplements, Fruit and Vegetable Juices, Kidney metabolism, Liver metabolism, Minerals metabolism
- Abstract
We evaluated the impact of a supplemental acerola juice (unripe, ripe, and industrial) and its main pharmaceutically active components on the concentrations of minerals in the liver and kidney of mice fed with cafeteria diet. Swiss male mice were fed with a cafeteria (CAF) diet for 13 weeks. The CAF consisted of a variety of supermarket products with high energy content. Subsequently, animals received one of the following food supplements for 1 month: water, unripe acerola juice, ripe acerola juice, industrial acerola juice, vitamin C, or rutin. Mineral concentrations of the tissues were determined by particle-induced X-ray emission (PIXE). Our study suggests that the simultaneous intake of acerola juices, vitamin C, or rutin in association with a hypercaloric and hyperlipidic diet provides change in the mineral composition of organisms in the conditions of this study, which plays an important role in the antioxidant defenses of the body. This may help to reduce the metabolism of the fat tissue or even to reduce the oxidative stress.
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- 2015
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11. Effects of palatable cafeteria diet on cognitive and noncognitive behaviors and brain neurotrophins' levels in mice.
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Leffa DD, Valvassori SS, Varela RB, Lopes-Borges J, Daumann F, Longaretti LM, Dajori AL, Quevedo J, and Andrade VM
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- Animals, Brain drug effects, Cognition drug effects, Energy Intake physiology, Glial Cell Line-Derived Neurotrophic Factor biosynthesis, Male, Maze Learning drug effects, Maze Learning physiology, Mice, Nerve Growth Factors biosynthesis, Brain metabolism, Brain-Derived Neurotrophic Factor biosynthesis, Cognition physiology, Diet, High-Fat, Dietary Sucrose administration & dosage, Nerve Growth Factor biosynthesis
- Abstract
The consumption of palatable high-fat and high-sugar foods have increased dramatically over the past years. Overconsumption of calorically dense food contributes to increasing rates of overweight and obesity that are associated with psychiatry disorders, in particular mood and anxiety disorders. This study evaluated the impact of palatable cafeteria diet (CAF) intake on cognitive and noncognitive behaviors, as well as identified factors related to these behaviors through an evaluation of brain neurotrophic factor (BDNF, NGF, and GDNF) levels in hippocampus of mice. Male Swiss mice received two different diets during 13 weeks: standard chow (STA) and highly CAF. Posteriorly, forced swimming test (FST), tail suspension test (TST), plus-maze test (PMT), open-field tests (OFT), and object recognition task (ORT) were utilized as behavioral tests. In addition, brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and nerve growth factor (NGF) neurotrophins' levels were evaluated in hippocampus of mice. The results demonstrated that mice from the CAF group showed a decrease in the immobility time in the FST and TST. Besides, mice in the CAF group spent more time in the open arms of the PMT. No significant differences were observed in the cognitive behaviors, which were evaluated in the OFT and ORT. In addition, the CAF group showed that BDNF and NGF protein levels increased in the hippocampus of mice. In conclusion, our data suggest that the consumption of palatable high-fat and high-sugar foods induces antidepressant- and anxiolytic-like behaviors, which can be related with BDNF and NGF expression increases in hippocampus of mice in the CAF group.
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- 2015
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12. Anxious phenotypes plus environmental stressors are related to brain DNA damage and changes in NMDA receptor subunits and glutamate uptake.
- Author
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Réus GZ, Abaleira HM, Michels M, Tomaz DB, dos Santos MA, Carlessi AS, Matias BI, Leffa DD, Damiani AP, Gomes Vde C, Andrade VM, Dal-Pizzol F, Landeira-Fernadez J, and Quevedo J
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- Animals, Anxiety genetics, Anxiety pathology, Brain pathology, Depression genetics, Depression metabolism, Depression pathology, Excitatory Amino Acid Transporter 1 genetics, Excitatory Amino Acid Transporter 1 metabolism, Excitatory Amino Acid Transporter 2 genetics, Excitatory Amino Acid Transporter 2 metabolism, Glutamic Acid genetics, Rats, Rats, Wistar, Receptors, N-Methyl-D-Aspartate genetics, Species Specificity, Stress, Psychological genetics, Stress, Psychological pathology, Anxiety metabolism, Brain metabolism, DNA Damage, Glutamic Acid metabolism, Receptors, N-Methyl-D-Aspartate metabolism, Stress, Psychological metabolism
- Abstract
This study aimed at investigating the effects of chronic mild stress on DNA damage, NMDA receptor subunits and glutamate transport levels in the brains of rats with an anxious phenotype, which were selected to represent both the high-freezing (CHF) and low-freezing (CLF) lines. The anxious phenotype induced DNA damage in the hippocampus, amygdala and nucleus accumbens (NAc). CHF rats subjected to chronic stress presented a more pronounced DNA damage in the hippocampus and NAc. NMDAR1 were increased in the prefrontal cortex (PC), hippocampus and amygdala of CHF, and decreased in the hippocampus, amygdala and NAc of CHF stressed. NMDAR2A were decreased in the amygdala of the CHF and stressed; and increased in CHF stressed. NMDRA2A in the NAc was increased after stress, and decreased in the CLF. NMDAR2B were increased in the hippocampus of CLF and CHF. In the amygdala, there was a decrease in the NMDAR2B for stress in the CLF and CHF. NMDAR2B in the NAc were decreased for stress and increased in the CHF; in the PC NMDAR2B increased in the CHF. EAAT1 increased in the PC of CLF+stress. In the hippocampus, EAAT1 decreased in all groups. In the amygdala, EAAT1 decreased in the CLF+stress and CHF. EAAT2 were decreased in the PC for stress, and increased in CHF+control. In the hippocampus, the EAAT2 were increased for the CLF and decreased in the CLF+stress. In the amygdala, there was a decrease in the EATT2 in the CLF+stress and CHF. These findings suggest that an anxious phenotype plus stress may induce a more pronounced DNA damage, and promote more alterations in the glutamatergic system. These findings may help to explain, at least in part, the common point of the mechanisms involved with the pathophysiology of depression and anxiety., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
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13. Obesity promotes oxidative stress and exacerbates sepsis-induced brain damage.
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Vieira AA, Michels M, Florentino D, Nascimento DZ, Rezin GT, Leffa DD, Fortunato JJ, Dal-Pizzol F, Barichello T, Quevedo J, and Petronilho F
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- Animals, Blood-Brain Barrier pathology, Brain pathology, Capillary Permeability physiology, Disease Models, Animal, Rats, Rats, Wistar, Brain physiopathology, Obesity complications, Oxidative Stress physiology, Sepsis complications, Sepsis physiopathology
- Abstract
Sepsis is a severe clinical syndrome in which a system-wide inflammatory response follows initial attempts to eliminate pathogens. It is not novel that in sepsis the brain is one of the first organs affected which causes an increase in morbidity and mortality and its consequences may be exacerbated when associated with a diagnosis of chronic inflammation, such as in obesity. Thus, the aim of the present study is to evaluate the susceptibility to brain damage after sepsis in obese rats. During two months, Wistar rats, 60 days, 250-300g received hypercaloric nutrition to induce obesity. Sepsis was submitted to the cecal ligation and perforation (CLP) procedure and sham-operated rats was considered control group. The experimental groups were divided into Sham + Eutrophic, Sham + Obesity, CLP + Eutrophic and CLP + Obesity. Twelve and twenty four hours after surgery the blood brain barrier (BBB) permeability, nitrite/nitrate concentration, myeloperoxidase (MPO) activity, oxidative damage to lipids and proteins and superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in the hippocampus, cortex and prefrontal cortex. The data indicate that in obese rats subjected to sepsis occurs an increase of BBB permeability in different brain regions compared to eutrophic septic rats. This alteration reflected an increase of MPO activity, concentration of nitrite/nitrate, oxidative damage to lipids and proteins and an imbalance of SOD and CAT especially 24 hours after sepsis. It follows that obesity due to its pro-inflammatory phenotype can aggravate or accelerate the sepsis-induced damage in rat brain.
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- 2015
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14. Corrective effects of acerola (Malpighia emarginata DC.) juice intake on biochemical and genotoxical parameters in mice fed on a high-fat diet.
- Author
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Leffa DD, da Silva J, Daumann F, Dajori AL, Longaretti LM, Damiani AP, de Lira F, Campos F, Ferraz Ade B, Côrrea DS, and de Andrade VM
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- Animals, Ascorbic Acid analysis, Ascorbic Acid pharmacology, Body Weight drug effects, Comet Assay, Eating drug effects, Eating physiology, Glucose Tolerance Test, Male, Mice, Micronucleus Tests, Quercetin analysis, Quercetin pharmacology, Rutin analysis, Rutin pharmacology, Antioxidants pharmacology, Beverages, DNA Damage drug effects, Diet, High-Fat, Malpighiaceae chemistry
- Abstract
Acerola contains high levels of vitamin C and rutin and shows the corresponding antioxidant properties. Oxidative stress on the other hand is an important factor in the development of obesity. In this study, we investigated the biochemical and antigenotoxic effects of acerola juice in different stages of maturity (unripe, ripe and industrial) and its main pharmacologically active components vitamin C and rutin, when given as food supplements to obese mice. Initial HPLC analyses confirmed that all types of acerola juice contained high levels of vitamin C and rutin. DPPH tests quantified the antioxidant properties of these juices and revealed higher antioxidant potentials compared to pure vitamin C and rutin. In an animal test series, groups of male mice were fed on a standard (STA) or a cafeteria (CAF) diet for 13 weeks. The latter consisted of a variety of supermarket products, rich in sugar and fat. This CAF diet increased the feed efficiency, but also induced glucose intolerance and DNA damage, which was established by comet assays and micronucleus tests. Subsequently, CAF mice were given additional diet supplements (acerola juice, vitamin C or rutin) for one month and the effects on bone marrow, peripheral blood, liver, kidney, and brain were examined. The results indicated that food supplementation with ripe or industrial acerola juice led to a partial reversal of the diet-induced DNA damage in the blood, kidney, liver and bone marrow. For unripe acerola juice food supplementation, beneficial effects were observed in blood, kidney and bone marrow. Food supplementation with vitamin C led to decreased DNA damage in kidney and liver, whereas rutin supplementation led to decreased DNA damage in all tissue samples observed. These results suggest that acerola juice helps to reduce oxidative stress and may decrease genotoxicity under obesogenic conditions., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2014
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15. Acute and chronic administration of gold nanoparticles cause DNA damage in the cerebral cortex of adult rats.
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Cardoso E, Rezin GT, Zanoni ET, de Souza Notoya F, Leffa DD, Damiani AP, Daumann F, Rodriguez JC, Benavides R, da Silva L, Andrade VM, and da Silva Paula MM
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- Age Factors, Animals, Cerebral Cortex metabolism, Comet Assay, Dose-Response Relationship, Drug, Drug Administration Schedule, Energy Metabolism drug effects, Gold administration & dosage, Male, Metal Nanoparticles administration & dosage, Rats, Rats, Wistar, Cerebral Cortex drug effects, DNA Damage, Gold toxicity, Metal Nanoparticles toxicity
- Abstract
The use of gold nanoparticles is increasing in medicine; however, their toxic effects remain to be elucidated. Studies show that gold nanoparticles can cross the blood-brain barrier, as well as accumulate in the brain. Therefore, this study was undertaken to better understand the effects of gold nanoparticles on rat brains. DNA damage parameters were evaluated in the cerebral cortex of adult rats submitted to acute and chronic administration of gold nanoparticles of two different diameters: 10 and 30nm. During acute administration, adult rats received a single intraperitoneal injection of either gold nanoparticles or saline solution. During chronic administration, adult rats received a daily single injection for 28 days of the same gold nanoparticles or saline solution. Twenty-four hours after either single (acute) or last injection (chronic), the rats were euthanized by decapitation, their brains removed, and the cerebral cortices isolated for evaluation of DNA damage parameters. Our study showed that acute administration of gold nanoparticles in adult rats presented higher levels of damage frequency and damage index in their DNA compared to the control group. It was also observed that gold nanoparticles of 30nm presented higher levels of damage frequency and damage index in the DNA compared to the 10nm ones. When comparing the effects of chronic administration of gold nanoparticles of 10 and 30nm, we observed that occurred significant different index and frequency damage, comparing with control group. However, there is no difference between the 10 and 30nm groups in the levels of DNA damage for both parameters of the Comet assay. Results suggest that gold nanoparticles for both sizes cause DNA damage for chronic as well as acute treatments, although a higher damage was observed for the chronic one., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2014
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16. Long-term effects of ageing and ovariectomy on aversive and recognition memory and DNA damage in the hippocampus of female rats.
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Leffa DD, Damiani AP, Damazio DD, Guerra NP, Moretti M, de Brito GG, Boeck CR, Gavioli EC, and de Andrade VM
- Subjects
- Aging genetics, Aging psychology, Animals, Estradiol blood, Female, Ovariectomy, Rats, Rats, Wistar, Aging physiology, DNA Damage, Hippocampus physiology, Recognition, Psychology physiology
- Abstract
Objective: This study investigated the influence of ageing - in particular the decrease of gonadal hormone levels during the ageing process - on the memory and the levels of DNA damage in the hippocampus of female rats., Methods: Three groups of female Wistar rats were investigated: Group I consisted of non-ovariectomised, adult animals (6 months old); Group II consisted of non-ovariectomised, aged animals (18 months old); and Group III consisted of ovariectomised, aged animals (18 months old). The memory of the animals in these groups was examined via novel object recognition and inhibitory avoidance tests. The hippocampus tissue samples of all animals were obtained via biopsy and used to quantify the DNA damage using a Comet Assay., Results: According to our findings, the process of ageing results in a change during the behavioural tests. To prevent genotoxic damage to the hippocampus caused by the ageing process, lowered hormone levels seem to be part of a protective biochemical mechanism in the body of rats. Animals that were previously submitted to an ovariectomy adapted better to these lower levels of hormones., Conclusion: Our results indicate that ovariectomy can provide beneficial long-term effects on the memory. However, this could be specific to the kind of memory examined, as the aversive memory deficits caused by ageing were not affected by ovariectomy.
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- 2014
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17. Methylmalonic acid administration induces DNA damage in rat brain and kidney.
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Andrade VM, Dal Pont HS, Leffa DD, Damiani AP, Scaini G, Hainzenreder G, Streck EL, Ferreira GC, and Schuck PF
- Subjects
- Animals, Brain drug effects, Caspase 3 metabolism, Cell Count, Gentamicins administration & dosage, Gentamicins toxicity, Kidney drug effects, Methylmalonic Acid administration & dosage, Methylmalonic Acid therapeutic use, Rats, Wistar, Tumor Suppressor Protein p53 metabolism, Brain pathology, DNA Damage, Kidney pathology, Methylmalonic Acid toxicity
- Abstract
Accumulation of methylmalonic acid (MMA) in tissues and biological fluids is the biochemical hallmark of methylmalonic aciduria. Affected patients present renal failure and severe neurological findings. Considering that the underlying pathomechanisms of tissue damage are not yet understood, in the present work we assessed the in vivo e in vitro effects of MMA on DNA damage in brain and kidney, as well as on p53 and caspase 3 levels, in the presence or absence of gentamicin (acute renal failure model). For in vitro studies, tissue prisms were incubated in the presence of different concentrations of MMA and/or gentamicin for one hour. For in vivo studies, animals received a single injection of gentamicin (70 mg/kg) and/or three injections of MMA (1.67 μmol/g; 11 h interval between injections). The animals were killed 1 h after the last MMA injection. Controls received saline in the same volumes. DNA damage was analyzed by the comet assay. We found that MMA and gentamicin alone or combined in vitro increased DNA damage in cerebral cortex and kidney of rats. Furthermore, MMA administration increased DNA damage in both brain and kidney. Gentamicin per se induced DNA damage only in kidney, and the association of MMA plus gentamicin also caused DNA damage in cerebral cortex and kidney. On the other hand, p53 and caspase 3 levels were not altered by the administration of MMA and/or gentamicin. Our findings provide evidence that DNA damage may contribute to the neurological and renal damage found in patients affected by methylmalonic aciduria.
- Published
- 2014
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18. Acerola (Malpighia emarginata DC.) juice intake protects against alterations to proteins involved in inflammatory and lipolysis pathways in the adipose tissue of obese mice fed a cafeteria diet.
- Author
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Dias FM, Leffa DD, Daumann F, Marques Sde O, Luciano TF, Possato JC, de Santana AA, Neves RX, Rosa JC, Oyama LM, Rodrigues B, de Andrade VM, de Souza CT, and de Lira FS
- Subjects
- Administration, Oral, Animals, Ascorbic Acid administration & dosage, Diet, Drug Evaluation, Preclinical, Energy Intake, Epididymis metabolism, Epididymis pathology, Fruit chemistry, Humans, Inflammation Mediators metabolism, Male, Mice, Mice, Obese, Obesity, Anti-Inflammatory Agents administration & dosage, Cytokines metabolism, Intra-Abdominal Fat metabolism, Lipolysis, Malpighiaceae chemistry, Plant Extracts administration & dosage
- Abstract
Background: Obesity has been studied as a metabolic and an inflammatory disease and is characterized by increases in the production of pro-inflammatory adipokines in the adipose tissue.To elucidate the effects of natural dietary components on the inflammatory and metabolic consequences of obesity, we examined the effects of unripe, ripe and industrial acerola juice (Malpighia emarginata DC.) on the relevant inflammatory and lipolysis proteins in the adipose tissue of mice with cafeteria diet-induced obesity., Materials/methods: Two groups of male Swiss mice were fed on a standard diet (STA) or a cafeteria diet (CAF) for 13 weeks. Afterwards, the CAF-fed animals were divided into five subgroups, each of which received a different supplement for one further month (water, unripe acerola juice, ripe acerola juice, industrial acerola juice, or vitamin C) by gavage. Enzyme-linked immunosorbent assays, Western blotting, a colorimetric method and histology were utilized to assess the observed data., Results: The CAF water (control obese) group showed a significant increase in their adiposity indices and triacylglycerol levels, in addition to a reduced IL-10/TNF-α ratio in the adipose tissue, compared with the control lean group. In contrast, acerola juice and Vitamin C intake ameliorated the weight gain, reducing the TAG levels and increasing the IL-10/TNF-α ratio in adipose tissue. In addition, acerola juice intake led to reductions both in the level of phosphorylated JNK and to increases in the phosphorylation of IκBα and HSLser660 in adipose tissue., Conclusions: Taken together, these results suggest that acerola juice reduces low-grade inflammation and ameliorates obesity-associated defects in the lipolytic processes.
- Published
- 2014
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19. Evaluation of the protective effect of Ilex paraguariensis and Camellia sinensis extracts on the prevention of oxidative damage caused by ultraviolet radiation.
- Author
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Barg M, Rezin GT, Leffa DD, Balbinot F, Gomes LM, Carvalho-Silva M, Vuolo F, Petronilho F, Dal-Pizzol F, Streck EL, and Andrade VM
- Subjects
- Animals, Comet Assay, DNA Damage drug effects, Male, Oxidative Stress drug effects, Protein Carbonylation drug effects, Rats, Rats, Wistar, Thiobarbituric Acid Reactive Substances metabolism, Antineoplastic Agents pharmacology, Antioxidants pharmacology, Camellia sinensis, Ilex paraguariensis, Plant Extracts pharmacology, Ultraviolet Rays adverse effects
- Abstract
We evaluated the effects green and mate teas on oxidative and DNA damages in rats exposed to ultraviolet radiation. Were utilized 70 adult male Wistar rats that received daily oral or topic green or mate tea treatment during exposed to radiation by seven days. After, animals were killed by decapitation. Thiobarbituric acid-reactive species levels, protein oxidative damage were evaluated in skin and DNA damage in blood. Our results show that the rats exposed to ultraviolet radiation presented DNA damage in blood and increased protein carbonylation and lipid peroxidation in skin. Oral and topic treatment with green tea and mate tea prevented lipid peroxidation, both treatments with mate tea also prevented DNA damage. However, only topic treatment with green tea and mate tea prevented increases in protein carbonylation. Our findings contribute to elucidate the beneficial effects of green tea and mate tea, here in demonstrated by the antioxidant and antigenotoxic properties presented by these teas., (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Published
- 2014
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20. Cognitive dysfunction in depression: lessons learned from animal models.
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Reus GZ, Abelaira HM, Leffa DD, and Quevedo J
- Subjects
- Animals, Humans, Cognition Disorders etiology, Depression complications, Disease Models, Animal
- Abstract
Major depression is a serious public health problem and one of the most common psychiatric disorders, and it is estimated that millions of people are affected worldwide. In addition, patients having depression present cognitive impairments, which could influence treatment adherence and long-term outcomes. Although, studies have shown that alterations in the hypothalamic-pituitary-adrenal axis, in inflammatory and antioxidant systems, and changes in intracellular pathways are involved in the cognitive impairment verified in depressive patients, it was unclear how these alterations occur. In this context, animal models of psychiatric disorders are revealed as good alternatives for the study of pathophysiology of these and associated factors. Thus, this review will highlight studies with animal models that have helped in understanding the mechanisms involved in cognitive impairment associated with depression, as well as focus on effective treatments that assist in improving both depression and cognition.
- Published
- 2014
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21. L-tyrosine induces DNA damage in brain and blood of rats.
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De Prá SD, Ferreira GK, Carvalho-Silva M, Vieira JS, Scaini G, Leffa DD, Fagundes GE, Bristot BN, Borges GD, Ferreira GC, Schuck PF, Andrade VM, and Streck EL
- Subjects
- Animals, Comet Assay, Oxidative Stress drug effects, Rats, Rats, Wistar, Tyrosine Transaminase genetics, Tyrosinemias chemically induced, Brain drug effects, DNA Damage physiology, Tyrosine toxicity
- Abstract
Mutations in the tyrosine aminotransferase gene have been identified to cause tyrosinemia type II which is inherited in an autosomal recessive manner. Studies have demonstrated that an excessive production of ROS can lead to reactions with macromolecules, such as DNA, lipids, and proteins. Considering that the L-tyrosine may promote oxidative stress, the main objective of this study was to investigate the in vivo effects of L-tyrosine on DNA damage determined by the alkaline comet assay, in brain and blood of rats. In our acute protocol, Wistar rats (30 days old) were killed 1 h after a single intraperitoneal L-tyrosine injection (500 mg/kg) or saline. For chronic administration, the animals received two subcutaneous injections of L-tyrosine (500 mg/kg, 12-h intervals) or saline administered for 24 days starting at postnatal day (PD) 7 (last injection at PD 31), 12 h after the last injection, the animals were killed by decapitation. We observed that acute administration of L-tyrosine increased DNA damage frequency and damage index in cerebral cortex and blood when compared to control group. Moreover, we observed that chronic administration of L-tyrosine increased DNA damage frequency and damage index in hippocampus, striatum, cerebral cortex and blood when compared to control group. In conclusion, the present work demonstrated that DNA damage can be encountered in brain from animal models of hypertyrosinemia, DNA alterations may represent a further means to explain neurological dysfunction in this inherited metabolic disorder and to reinforce the role of oxidative stress in the pathophysiology of tyrosinemia type II.
- Published
- 2014
- Full Text
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22. Oxidative stress in mice treated with antileishmanial meglumine antimoniate.
- Author
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Bento DB, de Souza B, Steckert AV, Dias RO, Leffa DD, Moreno SE, Petronilho F, de Andrade VM, Dal-Pizzol F, and Romão PR
- Subjects
- 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, Antiprotozoal Agents pharmacology, Meglumine pharmacology, Organometallic Compounds pharmacology, Oxidative Stress drug effects
- 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., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
- Full Text
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23. DNA damage induced by phenylalanine and its analogue p-chlorophenylalanine in blood and brain of rats subjected to a model of hyperphenylalaninemia.
- Author
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Simon KR, Dos Santos RM, Scaini G, Leffa DD, Damiani AP, Furlanetto CB, Machado JL, Cararo JH, Macan TP, Streck EL, Ferreira GC, Andrade VM, and Schuck PF
- Subjects
- Animals, Brain drug effects, Fenclonine blood, Male, Phenylalanine analogs & derivatives, Phenylalanine blood, Phenylalanine Hydroxylase deficiency, Phenylalanine Hydroxylase genetics, Phenylalanine Hydroxylase metabolism, Phenylketonurias blood, Phenylketonurias genetics, Rats, Rats, Wistar, Brain metabolism, DNA Damage drug effects, Fenclonine metabolism, Phenylalanine administration & dosage, Phenylketonurias metabolism
- Abstract
Phenylketonuria (PKU) is a disease caused by a deficiency of phenylalanine hydroxylase (PAH), resulting in an accumulation of phenylalanine (Phe) in the brain tissue, cerebrospinal fluid, and other tissues of PKU patients. Considering that high levels of Phe are associated with neurological dysfunction and that the mechanisms underlying the neurotoxicity in PKU remain poorly understood, the main objective of this study was to investigate the in vivo and in vitro effects of Phe on DNA damage, as determined by the alkaline comet assay. The results showed that, compared to control group, the levels of DNA migration were significantly greater after acute administration of Phe, p-chlorophenylalanine (p-Cl-Phe, an inhibitor of PAH), or a combination thereof in cerebral cortex and blood, indicating DNA damage. These treatments also provoked increase of carbonyl content. Additionally, when Phe or p-Cl-Phe was present in the incubation medium, we observed an increase in the frequency and index of DNA damage in the cerebral cortex and blood, without affecting lactate dehydrogenase (LDH) release. Our in vitro and in vivo findings indicate that DNA damage occurs in the cerebral cortex and blood of rats receiving Phe, suggesting that this mechanism could be, at least in part, responsible for the neurological dysfunction in PKU patients.
- Published
- 2013
- Full Text
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24. Effects of acute and chronic administration of fenproporex on DNA damage parameters in young and adult rats.
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Gonçalves CL, Rezin GT, Ferreira GK, Jeremias IC, Cardoso MR, Valvassori SS, Munhoz BJ, Borges GD, Bristot BN, Leffa DD, Andrade VM, Quevedo J, and Streck EL
- Subjects
- Age Factors, Amphetamines administration & dosage, Animals, Comet Assay, DNA blood, DNA genetics, Injections, Intraperitoneal, Male, Rats, Rats, Wistar, Time Factors, Amphetamines toxicity, DNA Damage
- Abstract
Obesity is a chronic and multifactorial disease, whose prevalence is increasing in many countries. Pharmaceutical strategies for the treatment of obesity include drugs that regulate food intake, thermogenesis, fat absorption, and fat metabolism. Fenproporex is the second most commonly consumed amphetamine-based anorectic worldwide; this drug is rapidly converted in vivo into amphetamine, which is associated with neurotoxicity. In this context, the present study evaluated DNA damage parameters in the peripheral blood of young and adult rats submitted to an acute administration and chronic administration of fenproporex. In the acute administration, both young and adult rats received a single injection of fenproporex (6.25, 12.5 or 25 mg/kg i.p.) or vehicle. In the chronic administration, both young and adult rats received one daily injection of fenproporex (6.25, 12.5, or 25 mg/kg i.p.) or Tween for 14 days. 2 h after the last injection, the rats were killed by decapitation and their peripheral blood removed for evaluation of DNA damage parameters by alkaline comet assay. Our study showed that acute administration of fenproporex in young and adult rats presented higher levels of damage index and frequency in the DNA. However, chronic administration of fenproporex in young and adult rats did not alter the levels of DNA damage in both parameters of comet assay. The present findings showed that acute administration of fenproporex promoted damage in DNA, in both young and adult rats. Our results are consistent with other reports which showed that other amphetamine-derived drugs also caused DNA damage. We suggest that the activation of an efficient DNA repair mechanism may occur after chronic exposition to fenproporex. Our results are consistent with other reports that showed some amphetamine-derived drugs also caused DNA damage.
- Published
- 2013
- Full Text
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25. Evaluation of the mutagenic effect of the iodinated contrast medium Urografina® 292 using the micronucleus test in mouse bone marrow cells.
- Author
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Belle MB, Leffa DD, Mazzorana D, and De Andrade VM
- Subjects
- Animals, Contrast Media administration & dosage, Diatrizoate Meglumine administration & dosage, Dose-Response Relationship, Drug, Male, Mice, Mice, Inbred Strains, Micronucleus Tests methods, Bone Marrow Cells drug effects, Chromosome Aberrations chemically induced, Contrast Media toxicity, Diatrizoate Meglumine toxicity
- Abstract
Contrast media (CM) are frequently used in diagnostic radiology and in radiotherapy as a diagnostic tool and in treatment planning. Previous studies have demonstrated that these compounds induce chromosomal aberrations. This study evaluates the mutagenic effects induced by the contrast medium Urografina® 292 (meglumine amidotrizoate and sodium-ionic dimmer) in bone marrow cells (BMC) of mice in vivo. Micronuclei assay was performed in BMC of CF-1 mice injected with CM 1.5 and 3.0 mL/kg intravenous doses and 1.0, 2.0, 3.0 mL/kg intraperitoneal doses. The animals were beheaded 24 h after treatment by cervical dislocation, and femur BMC from each animal were used in the micronucleus test. The group treated with the highest intravenous injection of Urografina® 292 (3.0 mL/kg) presented an increase in the frequency of micronucleated polychromatic erythrocytes (MNPCEs) in relation at the control group (P<0.05). The results obtained after intraperitoneal administration of CM showed that all doses (1.0 mL/kg, 2.0 mL/kg and 3.0 mL/kg) increased the frequency of MNPCEs, being significantly different from the negative control (P< 0.01). The present results suggest that iodinated contrast media Urografina® 292 may cause a significant increase of cytogenetic damage in bone marrow cells of mice.
- Published
- 2013
- Full Text
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26. Effects of neuropeptide S on seizures and oxidative damage induced by pentylenetetrazole in mice.
- Author
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Ramos SF, Mendonça BP, Leffa DD, Pacheco R, Damiani AP, Hainzenreder G, Petronilho F, Dal-Pizzol F, Guerrini R, Calo' G, Gavioli EC, Boeck CR, and de Andrade VM
- Subjects
- Animals, Behavior, Animal, Lipid Peroxidation, Male, Mice, Neuropeptides therapeutic use, Seizures metabolism, Neuropeptides pharmacology, Oxidative Stress drug effects, Pentylenetetrazole toxicity, Seizures drug therapy
- Abstract
Neuropeptide S (NPS) and its receptor were recently discovered in the central nervous system. In rodents, NPS promotes hyperlocomotion, wakefulness, anxiolysis, anorexia, and analgesia and enhances memory when injected intracerebroventricularly (i.c.v.). Herein, NPS at different doses (0.01, 0.1 and 1nmol) was i.c.v. administered in mice challenged with pentylenetetrazole (PTZ; 60mg/kg) repeatedly injected. Aiming to assess behavioral alterations and oxidative damage to macromolecules in the brain, NPS was injected 5min prior to the last dose of PTZ. The administration of NPS only at 1nmol increased the duration of seizures evoked by PTZ, without modifying frequency and latency of seizures. Biochemical analysis revealed that NPS attenuated PTZ-induced oxidative damage to proteins and lipids in the hippocampus and cerebral cortex. In contrast, the administration of NPS to PTZ-treated mice increased DNA damage in the hippocampus, but not cerebral cortex. In conclusion, this is the first evidence of the potential proconvulsive effects of NPS in mice. The protective effects of NPS against lipid and protein oxidative damage in the mouse hippocampus and cerebral cortex evoked by PTZ-induced seizures are quite unexpected. The present findings were discussed analyzing the paradoxical effects of NPS: facilitation of convulsive behavior and protection against oxidative damage to lipids and proteins., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
- Full Text
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27. DNA damage in an animal model of maple syrup urine disease.
- Author
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Scaini G, Jeremias IC, Morais MO, Borges GD, Munhoz BP, Leffa DD, Andrade VM, Schuck PF, Ferreira GC, and Streck EL
- Subjects
- Amino Acids, Branched-Chain administration & dosage, Amino Acids, Branched-Chain adverse effects, Animals, Antioxidants pharmacology, Antioxidants therapeutic use, Brain drug effects, Brain metabolism, Brain pathology, Disease Models, Animal, Male, Maple Syrup Urine Disease chemically induced, Maple Syrup Urine Disease drug therapy, Oxidative Stress drug effects, Rats, Rats, Wistar, DNA Damage drug effects, Maple Syrup Urine Disease genetics
- Abstract
Maple syrup urine disease is an inborn error of metabolism caused by a severe deficiency of the branched chain alpha-ketoacid dehydrogenase complex. Neurological dysfunction is a common finding in patients with maple syrup urine disease. However, the mechanisms underlying the neuropathology of brain damage in this disorder are poorly understood. In this study, we investigated whether acute or chronic administration of a branched chain amino acid pool (leucine, isoleucine and valine) causes transient DNA damage, as determined by the alkaline comet assay, in the brain and blood of rats during development and whether antioxidant treatment prevented the alterations induced by branched chain amino acids. Our results showed that the acute administration of branched chain amino acids increased the DNA damage frequency and damage index in the hippocampus. However, the chronic administration of branched chain amino acids increased the DNA damage frequency and damage index in both the hippocampus and the striatum, and the antioxidant treatment was able to prevent DNA damage in the hippocampus and striatum. The present study demonstrated that metabolite accumulation in MSUD induces DNA damage in the hippocampus and striatum and that it may be implicated in the neuropathology observed in the affected patients. We demonstrated that the effect of antioxidant treatment (N-acetylcysteine plus deferoxamine) prevented DNA damage, suggesting the involvement of oxidative stress in DNA damage., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
28. Prenatal exposure to cigarette smoke causes persistent changes in the oxidative balance and in DNA structural integrity in rats submitted to the animal model of schizophrenia.
- Author
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Fraga DB, Deroza PF, Ghedim FV, Steckert AV, De Luca RD, Silverio A, Cipriano AL, Leffa DD, Borges GD, Quevedo J, Pinho RA, Andrade VM, Dal-Pizzol F, and Zugno AI
- Subjects
- Animals, Female, Ketamine, Male, Models, Animal, Pregnancy, Prenatal Exposure Delayed Effects metabolism, Prenatal Exposure Delayed Effects physiopathology, Rats, Rats, Wistar, DNA metabolism, DNA Damage, Lipid Peroxidation, Schizophrenia metabolism, Schizophrenia physiopathology, Tobacco Smoke Pollution adverse effects
- Abstract
Epidemiological studies have indicated that prenatal exposure to environmental insults can bring an increased risk of schizophrenia. The objective of our study was to determine biochemical parameters in rats exposed to cigarette smoke (CS) in the prenatal period, evaluated in adult offspring submitted to animal model of schizophrenia induced by acute subanaesthetic doses of ketamine (5 mg/kg, 15 mg/kg and 25 mg/kg). Pregnant female Wistar rats were exposed to 12 commercially filtered cigarettes per day, daily for a period of 28 days. We evaluated the oxidative damage in lipid and protein in the rat brain, and DNA damage in the peripheral blood of male adult offspring rats. To determine oxidative damage in the lipids, we measured the formation of thiobarbituric acid reactive species (TBARS) and the oxidative damage to the proteins was assessed by the determination of carbonyl groups content. We also evaluated DNA damage using single-cell gel electrophoresis (comet assay). Our results showed that rats exposed to CS in the prenatal period presented a significant increase of the lipid peroxidation, protein oxidation and DNA damage in adult age. We can observe that the animals submitted at acute doses of ketamine also presented an increase of the lipid peroxidation and protein oxidation at different doses and structures. Finally, we suggest that exposure to CS during the prenatal period affects two essential cerebral processes during development: redox regulation and DNA integrity, evaluated in adult offspring. These effects can leads to several neurochemical changes similar to the pathophysiology of schizophrenia., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
29. Evaluation of the genotoxic and antigenotoxic potential of Melissa officinalis in mice.
- Author
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de Carvalho NC, Corrêa-Angeloni MJ, Leffa DD, Moreira J, Nicolau V, de Aguiar Amaral P, Rossatto AE, and de Andrade VM
- Abstract
Melissa officinalis (L.) (Lamiaceae), a plant known as the lemon balm, is native to the east Mediterranean region and west Asia. Also found in tropical countries, such as Brazil, where it is popularly known as "erva-cidreira" or "melissa", it is widely used in aqueous- or alcoholic-extract form in the treatment of various disorders. The aim was to investigate in vivo its antigenotoxicity and antimutagenicity, as well as its genotoxic/mutagenic potential through comet and micronucleus assaying. CF-1 male mice were treated with ethanolic (Mo-EE) (250 or 500 mg/kg) or aqueous (Mo-AE) (100 mg/kg) solutions of an M. officinalis extract for 2 weeks, prior to treatment with saline or Methyl methanesulfonate (MMS) doses by intraperitoneal injection. Irrespective of the doses, no genotoxic or mutagenic effects were observed in blood and bone-marrow samples. Although Mo-EE exerted an antigenotoxic effect on the blood cells of mice treated with the alkylating agent (MMS) in all the doses, this was not so with Mo-AE. Micronucleus testing revealed the protector effect of Mo-EE, but only when administered at the highest dose. The implication that an ethanolic extract of M. officinalis has antigenotoxic/antimutagenic properties is an indication of its medicinal relevance.
- Published
- 2011
- Full Text
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30. Evaluation of the genotoxic potential of the mineral coal tailings through the Helix aspersa (Müller, 1774).
- Author
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Leffa DD, Damiani AP, da Silva J, Zocche JJ, dos Santos CE, Boufleur LA, Dias JF, and de Andrade VM
- Subjects
- Animals, Coal Mining, Comet Assay, DNA Damage, Helix, Snails genetics, Coal toxicity, Environmental Monitoring methods, Helix, Snails drug effects, Minerals toxicity, Mutagens toxicity
- Abstract
Coal mining is an activity with a high potential for environmental pollution. Coal has been described as the most significant pollutant of all the fossil fuels, containing a heterogeneous mixture. Many elements present in coal byproducts as well as coal tailings are rich in potentially toxic and genotoxic metals, which ultimately lead to profound changes in cells, tissues, populations, and ecosystems. The purpose of this study was to assess the genotoxic potential of the mineral coal tailings using the land snail Helix aspersa. Animals were divided in three groups, clustered in plexiglass cages: control (animals fed with organic lettuce), coal tailings (animals living in a layer of pyrite tailings and fed with organic lettuce), and mine lettuce (animals fed with lettuce grown in an area located in a deposit of coal tailings). The hemolymph was collected at different exposure times (24 h, 48 h, 72 h, 96 h, 1 week, 2 weeks, 3 weeks, and 1 month) for comet assay analyses. Results showed that the animals of the coal tailings and mine lettuce groups presented higher levels of DNA damage in relation to the control group at all exposure times, but with a peak of DNA damage in 48 h and 96 h. These results demonstrate that the coal pyrite tailings are potentially genotoxic and that H. aspersa has proven to be a sensitive instrument for a better risk assessment of environmental pollution.
- Published
- 2010
- Full Text
- View/download PDF
31. DNA damage after acute and chronic treatment with malathion in rats.
- Author
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Réus GZ, Valvassori SS, Nuernberg H, Comim CM, Stringari RB, Padilha PT, Leffa DD, Tavares P, Dagostim G, Paula MM, Andrade VM, and Quevedo J
- Subjects
- Animals, Carcinogens, Comet Assay, DNA blood, Hippocampus chemistry, Hippocampus drug effects, Male, Micronucleus Tests, Mutagens, Rats, Rats, Wistar, DNA Damage drug effects, Insecticides administration & dosage, Malathion administration & dosage, Malathion toxicity
- Abstract
Malathion is an insecticide widely used in agriculture and in public health programs that when used indiscriminately in large amounts can cause environmental pollution and risk to human health. However, it is possible that during the metabolism of malathion, reactive oxygen species can be generated, and malathion may produce oxidative stress in intoxicated rats that can be responsible for alterations in DNA molecules related in some studies. As a result, the present study aimed to investigate the DNA damage of cerebral tissue and peripheral blood in rats after acute and chronic malathion exposure. We used single cell gel electrophoresis (Comet assay) to measure early damage in hippocampus and peripheral blood and the Micronucleus test in total erythrocytes samples. Malathion was administered intraperitoneally once a day for one day (acute) or for 28 days (chronic) protocols (in both protocols, malathion was administered at 25, 50, 100, and 150 mg/kg). Our results showed that malathion (100 and 150 mg/kg) increased the DNA damage index in the peripheral blood and in the hippocampus after both chronic and acute treatment. Malathion increased the frequency of micronuclei only in chronic treatment at 150 mg/kg dose, and induced a cytotoxic dose-dependent decrease in the frequency of polychromatic erythrocytes in the peripheral blood of rats. In conclusion, since malathion increased both the peripheral blood and hippocampus DNA damage index using the Comet assay and increased the frequency of micronuclei in the total peripheral blood, it can be regarded as a potential mutagen/carcinogenic agent.
- Published
- 2008
- Full Text
- View/download PDF
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