N-Acetylcysteine Attenuates Cisplatin Toxicity in the Cerebrum and Lung of Young Rats with Artificially Induced Protein Deficiency.

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.

Oleic acid reduces oxidative stress in rat brain induced by some anticancer drugs.

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.

Oseltamivir induces favorable response on oxidative damage in the brain of rats treated with Bezafibrate.

AIM: The purpose was to measure the effect of Oseltamivir on oxidative biomarkers and dopaminergic and serotonergic systems in brain of rats with induced hypotriglyceridemia by Bezafibrate.Male young Wistar rats were treated as follows: group 1, NaCl 0.9%, (Controls); group 2, Oseltamivir (100 mg/kg); group 3, single dose of Bezafibrate (150 mg/kg); group 4, four dose of Bezafibrate; group 5, single dose of Bezafibrate + Oseltamivir and group 6, four doses of Bezafibrate + Oseltamivir. Drugs were given orally. Triglycerides, Dopamine, 5-hydroxyindoleacetic acid (5-HIAA), Glutathione (GSH), Hydrogen peroxide (H2O2), lipid peroxidation, as well as total ATPase activity were measured using validated methods. RESULTS: Oseltamivir treated animals showed lower GSH and lipid peroxidation levels and an increment in 5-HIAA in the three evaluated brain regions. Treatment with Oseltamivir also reduces H2O2 in the cortex and cerebellum/medulla oblongata. ATPase enzyme increased in these regions in the groups that were administered with Bezafibrate in repeated doses and in combination with Oseltamivir in single dose. Dopamine concentrations decreased in groups treated with Oseltamivir in the three evaluated regions. Also, there was a decrease in dopamine concentrations in the cerebellum/medulla oblongata of the animals treated with the combination of Oseltamivir and Bezafibrate.Innovation and conclusion: Animals with bezafibrate induced hypo-triglyceridemia that received Oseltamivir, either in single or repeated doses, have a higher improvement of their antioxidant activity and also experienced changes in the dopaminergic and serotonergic system in their brain, intending establish the beneficial of joint administration of both drugs in obese patients.

Folic acid increases levels of GHS in brain of rats with oxidative stress induced with 3-nitropropionic acid.

Aim: This study tested the hypothesis that folic acid (FA) modulates biogenic amines and protects the brain against oxidative stress induced by 3-nitropropionic acid (3NPA).Methods: Male Wistar rats received (groups of six) for 5 d: FA (50 mg/kg); 3NPA (10 mg/kg); or FA +3NPA. At last day, rats were sacrificed, and their brain was obtained to measure the levels of dopamine, 5-hydroxiindol acetic acid (5-HIAA). Reduced glutathione (GSH), total ATPase, H2O2 and lipid peroxidation were measured.Results: GSH increased significantly in cortex of rats treated with FA. ATPase increased significantly in cerebellum/medulla oblongata and decreased in cortex of animal treated with 3NPA. 5-HIAA increased in striatum of rats that received 3NPA alone or combined with FA.Conclusion: 3NPA generates free radicals such effect can be counteracted with FA administration since this folate increases antioxidant capacity and modulates biogenic amines.

Biochemical and histological changes produced by sweeteners and cytarabine in the brain of young rats.

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.

Effect of cerebrolysin on dopaminergic neurodegeneration of rat with oxidative stress induced by 3-nitropropionic acid.

The study tested the hypothesis that cerebrolysin protects the brain from free radicals in rats treated with 3-nitropropionic acid (3-NPA). To address this hypothesis, the levels of dopamine (DA) and some oxidative stress biomarkers were measured after administration of 3-NPA. Young male Fischer rats were treated for three days with cerebrolysin, 3-NPA or both substances. Their brains were extracted, and DA, lipid peroxidation (LP), glutathione (GSH), calcium, and H2O2 were measured using validated methods. In the cortex, hemispheres and cerebellum/medulla oblongata of the group treated with cerebrolysin and 3-NPA, the levels of DA and LP decreased. In addition, calcium and H2O2 levels decreased in the hemispheres of the same group, while GSH increased in cortex. The increased dopamine metabolism due to the administration of cerebrolysin led to increased formation of radical species and oxidative stress, especially when free radicals were generated by 3-NPA.

[RAPD-PCR characterization of Pseudomonas aeruginosa strains obtained from cystic fibrosis patients]. / Caracterización, por RAPD-PCR, de aislados de Pseudomonas aeruginosa obtenidos de pacientes con fibrosis quística.

OBJECTIVE: To characterize P. aeruginosa strains isolated from bronchoalveolar lavage fluid of cystic fibrosis (CF) patients over a 3 year period. MATERIAL AND METHODS: A prospective follow-up study was carried out in a population of cystic fibrosis patients. The random amplified polymorphic DNA (RAP.D) technique was used to amplify DNA of P. aeruginosa strains isolated from bronchoalveolar lavage fluid samples of five CF patients from the Servicio de Neumología y Cirugía del Tórax del Instituto Nacional de Pediatría (Mexico City Chest Clinic of the National Pediatrics Institute) in Mexico City, between June 1996 and June 2002. Amplification patterns were established for each isolate to accurately identify all strains and to carry out an epidemiological analysis of P. aeruginosa among the selected CF patients. RESULTS: Eighteen different DNA amplification patterns were defined and used to identify each P. aeruginosa strain isolated from the different bronchoalveolar lavage samples. No correlation was observed between the different P. aeruginosa strain genotypes and mucoid or non-mucoid phenotypes, as strains with different phenotypes showed similar amplification patterns. Several strains with different amplification patterns were identified in samples obtained from the same patient, suggesting coinfection with ore than one P. aeruginosa strain. Two siblings with CF shared similargenotypes, suggesting the occurrence of cross- contamination. Similar genotypes of P. aeruginosa strains were isolated throughout the study period. CONCLUSION: Genotypic characterization of P. aeruginosa strains in CF patients allows more accurate epidemiological analyses of this important host-agent relationship.

Caracterización, por RAPD-PCR, de aislados de Pseudomonas aeruginosa obtenidos de pacientes con fibrosis quística / RAPD-PCR characterization of Pseudomonas aeruginosa strains obtained from cystic fibrosis patients

OBJETIVO: Caracterizar a las cepas de P aeruginosa aisladas de lavados broncoalveolares de pacientes con fibrosis quística a lo largo de un periodo de tres años. MATERIAL Y MÉTODOS: Estudio prospectivo, de seguimiento de una población de pacientes con fibrosis quística. Se utilizó la técnica de la amplificación del ADN empleando PCR con bajas condiciones de especificidad (Random amplified polymorphic DNA, RAPD-PCR) para la amplificación del ADN de cepas de P aeruginosa aisladas de lavados broncoalveolares de cinco pacientes con fibrosis quística, provenientes del Servicio de Neumología y Cirugía del Tórax del Instituto Nacional de Pediatría de la Ciudad de México, en el periodo de junio de 1996 a junio de 2002; se establecieron los patrones de amplificación de cada aislamiento, lo que permitió la identificación precisa de todas las cepas aisladas y el estudio de la epidemiología de P aeruginosa en los pacientes seleccionados con dicha enfermedad. RESULTADOS: Se definieron 18 patrones de amplificación del ADN que permitieron identificar a cada cepa de P aeruginosa aislada en las diferentes muestras de lavado broncoalveolar; no se encontró relación entre el fenotipo de P aeruginosa (mucoide o no mucoide) y el genotipo de cada aislamiento, ya que cepas con fenotipos distintos mostraron patrones de amplificación semejantes; en nuestros pacientes se identificaron cepas con patrones de amplificación distintos a partir de una misma muestra, lo que sugiere la presencia de infecciones simultáneas por más de una cepa de P aeruginosa; se demostró que dos hermanos con la enfermedad compartían cepas con genotipos semejantes, lo que sugiere una contaminación cruzada entre ambos, y se demostró el aislamiento de cepas de P aeruginosa con genotipos semejantes a lo largo de los periodos estudiados. CONCLUSIONES: La identificación mediante la caracterización genotípica de las cepas de P aeruginosa aisladas de los pacientes con fibrosis quística permite llevar a cabo estudios más precisos de la epidemiología de esta importante relación huésped-parásito.

Aislamiento de poblaciones de Serratia marcescens de origen clínico en dos institutos pediátricos / Isolation of populations of Serratia marcescens of clinical origin in two pediatrics institutions

Introudcción. Serratia marcescens es un patógeno oportunista en hospederos inmunocomprometidos y se asocia fundamentalmente a brotes intrahospitalarios con tasas de letalidad elevadas. El propósito del presente estudio fue tipificar 2 poblaciones de S. marcescens de origen clínico aisladas en 2 institutos pediátricos semejantes. Material y métodos. Se empleó el sistema de biotipificación propuesto por Grimont para la caracterización de 65 cepas del Hospital Infantil de México, originalmente clasificadas como Enterobacter sp y 35 cepas del Instituto Nacional de Pediatría aisladas en un brote intrahospitalario. Reesultados. El biogrupo más numeroso en ambas poblaciones fue el A 5/8 y de éste los biotipos A8a y A8b; se observaron variaciones en las proporciones de los biotipos identificados acordes al hospital de aislamiento, así como en los biotipos y patrones de resistencia a los antibióticos en cepas aisladas del mismo pacientes en muestras diferentes. Conclusiones. Del presente estudio se concluye que es importante que en los hospitales se realicen estudios epidemiológicos particulares de sus poblaciones de S. marcescens, pero es más importante aún que se lleve a cabo una correcta identificación de esta bacteria para valorar adecuadamente su importancia como patógeno oportunista en nuestro medio