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1.
Chem Biol Interact ; 398: 111086, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38825054

ABSTRACT

Oleic acid (OA) is a monounsaturated compound with many health-benefitting properties such as obesity prevention, increased insulin sensitivity, antihypertensive and immune-boosting properties, etc. The aim of this study was to analyze the effect of oleic acid (OA) and some anticancer drugs against oxidative damage induced by nitropropionic acid (NPA) in rat brain. Six groups of Wistar rats were treated as follows: Group 1, (control); group 2, OA; group 3, NPA + OA; group 4, cyclophosphamide (CPP) + OA; group 5, daunorubicin (DRB) + OA; and group 6, dexrazoxane (DXZ) + OA. All compounds were administered intraperitoneally route, every 24 h for 5 days. Their brains were extracted to measure lipoperoxidation (TBARS), H2O2, Ca+2, Mg+2 ATPase activity, glutathione (GSH) and dopamine. Glucose, hemoglobin and triglycerides were measured in blood. In cortex GSH increased in all groups, except in group 2, the group 4 showed the highest increase of this biomarker. TBARS decrease, and dopamine increase in all regions of groups 4, 5 and 6. H2O2 increased only in cerebellum/medulla oblongata of group 5 and 6. ATPase expression decreased in striatum of group 4. Glucose increased in group 6, and hemoglobin increased in groups 4 and 5. These results suggest that the increase of dopamine and the antioxidant effect of oleic acid administration during treatment with oncologic agents could result in less brain injury.


Subject(s)
Antineoplastic Agents , Brain , Glutathione , Oleic Acid , Oxidative Stress , Rats, Wistar , Animals , Oxidative Stress/drug effects , Oleic Acid/pharmacology , Brain/drug effects , Brain/metabolism , Rats , Male , Glutathione/metabolism , Antineoplastic Agents/pharmacology , Hydrogen Peroxide/metabolism , Nitro Compounds/pharmacology , Dopamine/metabolism , Propionates/pharmacology , Cyclophosphamide , Lipid Peroxidation/drug effects , Daunorubicin/pharmacology , Thiobarbituric Acid Reactive Substances/metabolism , Adenosine Triphosphatases/metabolism , Antioxidants/pharmacology
2.
Int J Mol Sci ; 25(11)2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38892427

ABSTRACT

Neurotoxicity is a major obstacle in the effectiveness of Cisplatin in cancer chemotherapy. In this process, oxidative stress and inflammation are considered to be the main mechanisms involved in brain and lung toxicity. The aim of the present work was to study the influence of the amount of protein on some oxidative parameters in the brain and lungs of rats treated with Cisplatin (CP) and N-Acetylcysteine (NAC) as neuroprotectors. Four groups of Wistar rats, each containing six animals, were fed with a protein diet at 7% for 15 days. Thereafter, the groups were given either a unique dose of CP® 5 mg/kg or NAC® 5 mg/kg as follows: group 1 (control), NaCl 0.9% vehicle; group 2, CP; group 3, NAC; and group 4, NAC + CP. The animals were sacrificed immediately after the treatments. Blood samples were collected upon sacrifice and used to measure blood triglycerides and glucose. The brain and lungs of each animal were obtained and used to assay lipid peroxidation (TBARS), glutathione (GSH), serotonin metabolite (5-HIAA), catalase, and the activity of Ca+2, and Mg+2 ATPase using validated methods. TBARS, H2O2, and GSH were found to be significantly decreased in the cortex and cerebellum/medulla oblongata of the groups treated with CP and NAC. The total ATPase showed a significant increase in the lung and cerebellum/medulla oblongata, while 5-HIAA showed the same tendency in the cortex of the same group of animals. The increase in 5-HIAA and ATPase during NAC and CP administration resulted in brain protection. This effect could be even more powerful when membrane fluidity is increased, thus proving the efficacy of combined NAC and CP drug therapy, which appears to be a promising strategy for future chemotherapy in malnourished patients.


Subject(s)
Acetylcysteine , Cisplatin , Lung , Rats, Wistar , Animals , Cisplatin/adverse effects , Cisplatin/toxicity , Acetylcysteine/pharmacology , Rats , Lung/drug effects , Lung/metabolism , Lung/pathology , Lipid Peroxidation/drug effects , Oxidative Stress/drug effects , Male , Cerebrum/drug effects , Cerebrum/metabolism , Glutathione/metabolism , Neuroprotective Agents/pharmacology , Antineoplastic Agents/adverse effects
3.
Nutr Hosp ; 35(1): 194-200, 2018 Feb 13.
Article in English | MEDLINE | ID: mdl-29565169

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the effect of splenda and stevia on dopamine and 5-HIAA levels, and some biomarkers of oxidative stress in the presence of cytarabine. METHODS: Forty-eight young male Wistar rats each with a weight of 80 g (four weeks of age), distributed in six groups of eight animals each, were treated as follows: group 1, control (NaCl 0.9% vehicle); group 2, cytarabine (0.6 g/kg); group 3, stevia (0.6 g/kg); group 4, cytarabine + stevia; group 5, splenda; and group 6, cytarabine + splenda. Cytarabine was given intravenously (IV) while stevia and splenda were administered orally for five days, using orogastric tube. At the end of treatment, the animals were sacrificed and glucose levels in blood were measured. The brains were dissected for histological analysis and homogenated to measure levels of dopamine, lipid peroxidation (TBARS), serotonin metabolite (5-HIAA), Na+, K+ ATPase activity, and glutathione (GSH), using validated methods. RESULTS: Sweeteners increased the glucose in animals that received cytarabine. Dopamine increased in cortex and decreased in striatum of animals that received stevia alone and combined with cytarabine. 5-HIAA decreased in striatum and cerebellum/medulla oblongata of animals that received sweeteners and cytarabine alone or combined. GSH increased in animals that received sweeteners and decreased with cytarabine. Lipoperoxidation decreased in groups that received sweeteners and cytarabine. Histopathological changes revealed marked degeneration of neuronal cells in animals treated with cytarabine. CONCLUSION: These results show that sweeteners as stevia or splenda may lead to the onset of unfavorable changes in dopamine and 5-HIAA. Antioxidant effects may be involved. Besides, histological changes revealed marked lesions of neuronal cells in experimental animals treated with cytarabine.


Subject(s)
Antimetabolites, Antineoplastic/pharmacology , Brain Chemistry/drug effects , Brain/anatomy & histology , Brain/drug effects , Cytarabine/pharmacology , Sweetening Agents/pharmacology , Animals , Dopamine/metabolism , Hydroxyindoleacetic Acid/metabolism , Male , Oxidative Stress/drug effects , Rats , Rats, Wistar , Stevia , Sucrose/analogs & derivatives
4.
Nutr. hosp ; 35(1): 194-200, ene.-feb. 2018. graf, ilus
Article in English | IBECS | ID: ibc-172108

ABSTRACT

Objective: The aim of this study was to evaluate the effect of splenda and stevia on dopamine and 5-HIAA levels, and some biomarkers of oxidative stress in the presence of cytarabine. Methods: Forty-eight young male Wistar rats each with a weight of 80 g (four weeks of age), distributed in six groups of eight animals each, were treated as follows: group 1, control (NaCl 0.9% vehicle); group 2, cytarabine (0.6 g/kg); group 3, stevia (0.6 g/kg); group 4, cytarabine + stevia; group 5, splenda; and group 6, cytarabine + splenda. Cytarabine was given intravenously (IV) while stevia and splenda were administered orally for five days, using orogastric tube. At the end of treatment, the animals were sacrificed and glucose levels in blood were measured. The brains were dissected for histological analysis and homogenated to measure levels of dopamine, lipid peroxidation (TBARS), serotonin metabolite (5-HIAA), Na+, K+ ATPase activity, and glutathione (GSH), using validated methods. Results: Sweeteners increased the glucose in animals that received cytarabine. Dopamine increased in cortex and decreased in striatum of animals that received stevia alone and combined with cytarabine. 5-HIAA decreased in striatum and cerebellum/medulla oblongata of animals that received sweeteners and cytarabine alone or combined. GSH increased in animals that received sweeteners and decreased with cytarabine. Lipoperoxidation decreased in groups that received sweeteners and cytarabine. Histopathological changes revealed marked degeneration of neuronal cells in animals treated with cytarabine. Conclusion: These results show that sweeteners as stevia or splenda may lead to the onset of unfavorable changes in dopamine and 5-HIAA. Antioxidant effects may be involved. Besides, histological changes revealed marked lesions of neuronal cells in experimental animals treated with cytarabine (AU)


Objetivo: el objetivo fue evaluar el efecto de edulcorantes (splenda y stevia) sobre los niveles de dopamina, acido 5-hidroxiindolacetico (HIAA) y algunos biomarcadores de estrés oxidativo en presencia de citarabina. Métodos: cuarenta y ocho ratas Wistar machos con un peso aproximado de 80 g (cuatro semanas de edad), distribuidas en seis grupos de ocho animales cada uno, fueron tratados como sigue: grupo 1, control (NaCl 0,9% vehículo); grupo 2, citarabina (0,6 g/kg); grupo 3, stevia (0,6 g/kg); grupo 4, citarabina + stevia; grupo 5, splenda; y el grupo 6, citarabina + splenda. La citarabina fue administrada por vía intravenosa y la stevia y la splenda, por vía oral durante cinco días, utilizando una sonda orogastrica. Al final del tratamiento, los animales fueron sacrificados y se midieron los niveles de glucosa en sangre. Los cerebros fueron disecados para su análisis histológico y homogenizados para medir los niveles de dopamina, peroxidacion lipidica (TBARS), metabolito de la serotonina (5-HIAA), actividad de la Na+, K+ ATPasa y glutatión (GSH), usando métodos validados. Resultados: los edulcorantes aumentaron la glucosa en los animales que recibieron citarabina. La dopamina aumento en la corteza y disminuyo en el estriado de los animales que recibieron stevia sola y combinada con citarabina. La 5-HIAA disminuyo en el estriado y el cerebelo/ medula oblongata de animales que recibieron edulcorantes y citarabina sola o combinada. El GSH se incrementó en los animales que recibieron edulcorantes. La lipoperoxidacion disminuyo en los grupos que recibieron edulcorantes y citarabina. Estudios histopatológicos revelaron una degeneración neuronal importante en animales tratados con citarabina. Conclusión: los resultados muestran que los edulcorantes como stevia o splenda pueden conducir a la aparición de cambios desfavorables en los niveles de dopamina y 5-HIAA. Los cambios histológicos revelaron, además, lesiones marcadas de células neuronales en animales tratados con citarabina (AU)


Subject(s)
Animals , Rats , Cerebrum , Cytarabine/pharmacokinetics , Sweetening Agents/pharmacokinetics , Drug Interactions , Disease Models, Animal , Dopamine , Receptors, Dopamine , Lipid Peroxidation , Blood Glucose , Oxidative Stress , Neurons
5.
Biomed Pharmacother ; 78: 210-215, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26898444

ABSTRACT

UNLABELLED: The aim of this work was to compare the effects of catechin (CAT), epicatechin (EPI) and N-ω-l-nitroarginine (L-NARG) on different endpoints of oxidative stress induced by quinolinic acid (QUIN) in a simple tissue preparation, rat striatal slices - with particular emphasis in the glutathione system - in order to provide revealing information on the antioxidant efficacy of these agents in an excitotoxic model. METHODS: Rat striatal slices were incubated for 1h in the presence of 100 µM QUIN and/or 85 µM CAT or EPI, or 100 µM L-NARG. Lipid peroxidation (LP) and the levels of reduced and oxidized glutathione (GSH and GSSG) were determined. RESULTS: The three agents tested completely blocked the QUIN-induced lipid peroxidation and recovered the QUIN-induced altered GSH/GSSG balance. No statistical differences were detected among the protective effects exerted by these antioxidants, suggesting similar efficacy and common antioxidant mechanisms. The antioxidant properties exhibited by these molecules on the excitotoxic model tested herein support an active role of glutathione and prompt their use as therapeutic tools in models of neurodegenerative disorders.


Subject(s)
Catechin/pharmacology , Corpus Striatum/pathology , Nitroarginine/pharmacology , Oxidative Stress/drug effects , Quinolinic Acid/toxicity , Animals , Glutathione Disulfide/metabolism , Lipid Peroxidation/drug effects , Lipids/chemistry , Male , Rats, Wistar
6.
Life Sci ; 135: 165-72, 2015 Aug 15.
Article in English | MEDLINE | ID: mdl-26135627

ABSTRACT

AIMS: This simple study was designed to investigate whether acute restraint stress can generate changes in behavioral tests and hippocampal endpoints of oxidative stress in rats, and if the antioxidant S-allyl cysteine (SAC) can prevent these alterations. MATERIALS AND METHODS: We evaluated motor activity, forced swimming and anxiety behavior, as well as the hippocampal levels of lipid peroxidation and the activities of glutathione-related enzymes in animals submitted to mild immobilization. The effect of SAC (100 mg/kg, i.p.), given to rats every day 30 min before starting the immobilization session, was also investigated. Immobilization (restraint) stress was induced for a period of 6 h per day for five consecutive days. KEY FINDINGS: Our results indicate that, under the tested conditions, acute restraint stimulates compensatory behavioral tasks (motor activity, anxiety and forced swimming) to counteract the stressing conditions prevailing, and selectively increased the levels of lipid peroxidation and the enzyme activities of glutathione-S-transferase (GST) and glutathione peroxidase (GPx) in the hippocampus also as adaptive responses. SAC exhibited preventive effects in the stressed group as it improved behavior, reduced lipid peroxidation and prevented the increase of GST and GPx activities, suggesting that this antioxidant blunted primary pro-oxidative stimuli induced by restraint stress. SIGNIFICANCE: Findings of this work also confirm that the use of antioxidants such as SAC can provide effective protection against the acute oxidative damage associated with anxiety produced by stressing conditions.


Subject(s)
Antioxidants/pharmacology , Behavior, Animal/drug effects , Cysteine/analogs & derivatives , Hippocampus/metabolism , Motor Activity/drug effects , Oxidative Stress/drug effects , Animals , Antineoplastic Agents/pharmacology , Cysteine/pharmacology , Hippocampus/pathology , Hippocampus/physiopathology , Male , Rats , Rats, Wistar , Restraint, Physical , Time Factors
7.
Proc West Pharmacol Soc ; 48: 118-21, 2005.
Article in English | MEDLINE | ID: mdl-16416675

ABSTRACT

The aim of this study was to analyze the effect of nutritional status and exposure to ozone on the activity of Na+/K+ ATPase and lipid peroxidation in rat brain. Male Wistar rats were fed 7% and 23% protein diets. Two groups were formed for each nutritional status: one group was exposed for 15 successive days to 0.75 ppm of ozone in air and the other was exposed to air. Subsequently, the brain was dissected and cortex, hemispheres, cerebellum and brainstem separately homogenized to measure the activity of thiobarbituric acid reactive substances (TBARS) and ATPase in the presence and absence of ouabain. The activity of Na+/K+ ATPase increased in cerebellum of well-nourished rats exposed to ozone, while total ATPase and TBARS decreased in all studied areas in the malnourished groups. These results suggest that nutritional status and exposure to ozone generate changes in lipid membrane composition, in turn changing the activity of sodium pump with similar consequences for brain metabolism.


Subject(s)
Brain/enzymology , Lipid Peroxidation/drug effects , Nutritional Status/physiology , Oxidants, Photochemical/toxicity , Ozone/toxicity , Sodium-Potassium-Exchanging ATPase/metabolism , Animals , Brain/drug effects , Male , Rats , Rats, Wistar , Thiobarbituric Acid Reactive Substances/metabolism , Weight Gain/drug effects
8.
Arch Med Res ; 35(4): 271-4, 2004.
Article in English | MEDLINE | ID: mdl-15325498

ABSTRACT

BACKGROUND: The aim of this study was to evaluate effects of pyridoxine and butylated hydroxytoluene (BHT) on lipid peroxidation and on levels of 5-hydroxytryptophan and serotonin. METHODS: Thirty rats (30 days of age) were used in the survey, measuring levels of lipid peroxidation (TBARS), hemoglobin, 5-hydroxytryptophan (5-HTP), and serotonin (5-HT) after intraperitoneal (i.p.) injections of 4 and 10 mg/kg/day of pyridoxine HCl during 20 days and a single dose of 2 microM/kg (440 microg) of BHT. RESULTS: Levels of TBARS and 5-HTP increased considerably (p <0.05) in all vitamin- and/or BHT-treated groups, and 5-HT increased partially (p <0.05) only in B(6) with or without BHT-treated groups compared with control group. CONCLUSIONS: Results suggest that pyridoxine plays a role in tryptophan metabolism, increasing production of 5-HTP.


Subject(s)
5-Hydroxytryptophan/metabolism , Brain/drug effects , Brain/metabolism , Pyridoxine/pharmacology , Serotonin/metabolism , Animals , Antioxidants/chemistry , Antioxidants/pharmacology , Butylated Hydroxytoluene/chemistry , Butylated Hydroxytoluene/pharmacology , Diet , Lipid Peroxidation , Rats , Rats, Wistar , Thiobarbituric Acid Reactive Substances/metabolism
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