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.

The administration of food supplemented with cocoa powder during nutritional recovery reduces damage caused by oxidative stress in rat brain.

Malnutrition contributes to the development of oxidative damage in the central nervous system. The selective administration of nutrients tends to show positive results in individuals who have suffered from malnutrition. To determine the effect of the administration of cocoa powder on the peroxidation of lipids and glutathione level during the nutritional recovery in brain, rats of 21 days old were subjected to a protocol that resembles malnutrition (MN) by feeding them with 60% of the daily food consumption of the control group (WN) and later to nutritional recovery with regular rodent feed (RFR) or added with cocoa (10 g of cocoa powder/kg of regular rodent feed) (CCR). Animals fed with regular rodent food showed significant reduction in brain glutathione: RFR (84.18 ± 6.38 ng/mg protein) vs. CCR (210.61 ± 50.10 ng/mg protein) and WN (186.55 ± 33.18 ng/mg protein), but with similar level to that of MN (92.12 ± 15.60 ng/mg protein). On the contrary, lipid peroxidation in RFR-fed animals increased RFR (1.32 ± 0.2 µM malondialdehyde/g of tissue), CCR (0.86 ± 0.07 µM malondialdehyde/g of tissue), WN (0.89 ± 0.09 µM malondialdehyde/g of tissue), but their thiobarbituric acid reactive substances concentration is similar to that of MN group (1.50 ± 0.2 µM malondialdehyde/g of tissue). Consumption of cocoa powder as a source of antioxidants favors the restoration of the concentration of glutathione and reduces the damage caused by oxidative stress during nutritional recovery in rat brain.

Comparison between types of cancer chemotherapies used in a private and a government-based hospital in Mexico.

We have compared the frequency and types of cancer chemotherapies used in a private hospital and in a government-based hospital in Mexico City. A retrospective study was conducted from January 2005 to December 2007, and therapeutic management determined in 415 cases reviewed by the attending physicians of the oncology service. In the government-based hospital, 60 different types of cancer were found among 273 patients diagnosed. Acute lymphoblastic leukemia (ALL) had the greatest incidence (30%), followed by Hodgkin's lymphoma (9%), retinoblastoma (7%), neuroblastoma (6%), and osteosarcoma (6%). The entire number of chemotherapy sessions was 7575. Drugs most frequently employed included etoposide (577), followed by methotrexate (575), vincristine (483), cyclophosphamide (312), and cytarabine (277). The economic status among these patients was mainly of limited resources and represented 80% of the total number of patients. The types of cancer found in the private hospital were similar, however the drugs used were predominantly cyclophosphamide (416), doxorubicin (382), 5-fluorouracil (368), paclitaxel (237) and cisplatin (128). The types of cancer were similar in both hospitals and reflected the incidence among the entire population in Mexico, since acute lymphoblastic leukemia, Hodgkin's lymphoma and retinoblastoma, were the types most represented. However, the treatment schemes differed; the chemotherapeutic agents used in the private hospital were rather more specific but significantly more expensive than those employed in the government hospital.

Effect of ivelip and sodium nitroprusside on 5-HT, glutathione and lipid peroxidation in normal and malnourished rat brain.

We examined the effect of experimental malnutrition and diet supplementation of parameters of central nervous system damage. Wistar rats were fed during 30 days and classified as malnourished (MN, 7% protein content diet) or well-nourished (WN, 23% protein content diet), were grouped and treated as follows: I-control; II-SNP (20 microg/kg); IIl-Ivelip (280 mg/kg) and IV-Ivelip + sodium nitroprusside (SNP). Levels of lipid peroxidation (TBARS), glutathione (GSH), tryptophan (Trp) and serotonin (5-HT) were assessed in brain by liquid chromatography. TBARS and GSH levels increased significantly (p < 0.05) in MN vs. WN rats that did not receive Ivelip. No significant differences were observed in TBARS and GSH among rats that received Ivelip or SNP. The weight of rats decreased significantly (p < 0.05) in all MN groups in relation to the WN groups. Hemoglobin (Hb) levels increased significantly (p < 0.05) in MN and WN groups that received Ivelip. 5-HT levels increased significantly (p < 0.05) in all MN groups. Trp levels increased significantly (p < 0.05) in the WN + Ivelip group vs. control. Early malnutrition induces changes in the metabolism of biogenic amines and this condition may promote oxidative injury of the brain.

Effect of nutritional status and ozone exposure on some biomarkers of oxidative stress in rat brain regions.

The aim of this study was to analyze the effect of nutritional condition and simulated exposure to ozone on Glutathione (GSH), the activity of Na+/K+ ATPase and lipid peroxidation in rat brain. Male Wistar rats were fed with 7% and 23% protein diets. Two groups were formed for each nutritional condition: one group was exposed for 15 successive days to 0.75 ppm of ozone and the other to air. Subsequently, the brain was dissected in cortex, hemispheres, cerebellum, and brainstem to measure the activity of thiobarbituric acid reactive substances (TBARS), ATPase, and levels of GSH. 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. The levels of GSH decreased significantly (P < 0.05) in the brain of rats fed with 7% of protein diet and exposed to ozone but increased in rats fed with normal diet and exposed to ozone. These results suggest that malnutrition causes alterations in the values of Na+/K+ ATPase, total ATPase, GSH, and lipid peroxidation, while ozone contributes to these modifications. As a consequence, both variables are involved in oxidative stress in the rat brain.

Effect of toluene and cresols on Na+,K+-ATPase, and serotonin in rat brain.

The objective of the present trial was to evaluate the effect of toluene and o-cresol, m-cresol, and p-cresol on serotonin (5-HT), its precursor 5-hydroxytryptophane (5-HTP), Na(+),K(+)-ATPase, total ATPase, and lipid peroxidation (TBARS) in rat brain. Evaluation of lipid peroxidation was realized by means of TBARS, determination of biogenic amines and enzymes assay was carried out in brain homogenate samples using HPLC and spectrophotometry, respectively. Five groups of male Wistar rats (200 g) were treated as follow: control, toluene, o-cresol, m-cresol, and p-cresol groups, which were administered 35 mg/kgi.p. of each compound, the control group was given only glycerine as vehicle. 5-HT and 5-HTP levels increased significantly (p < 0.001) in toluene and o-cresol groups. Lipid peroxidation increased significantly (p < 0.002) in all groups. A significant increase (p < 0.001) of Na(+),K(+)-ATPase was noted in the toluene and o-cresol groups, while this enzyme was reduced in the p-cresol group compared to the control group. Total ATPase showed significant differences in the p-cresol group, compared to the control group. Based in our results, it can be concluded that toluene and all cresols groups may increase lipid peroxidation and consequently induce changes in membrane fluidity.

Evaluación del desarrollo motor en función de género, estimulación disponible en el hogar y nivel socioeconómico en niños de 0 a 3 años de edad del área rural / Motor development in child from 0 to 3 years of age of the central rural area of the Mexican Republic, as a function at gender, socioeconomic level and stimulation available at home

Introducción. La edad en que los niños controlan sus movimientos se utiliza frecuentemente como indicador del nivel de desarrollo. El objetivo de este trabajo es evaluar el desarrollo motor grueso, de niños de 0 a 3 años de edad, en función de género, nivel socioeconómico y estimulación disponible en el hogar, y elaborar una escala de desarrollo aplicable a la población rural mexicana.Material y métodos. Se estudiaron 82 niños en los que se evaluó el desarrollo motor utilizando la escala para el diagnóstico del desarrollo de Gesell, modificada para su calificación por Cravioto. Se observó que utilizando esta forma de calificación, los niños se ubican por debajo de la norma propuesta por Gesell. Por esta razón, empleando el orden y la edad a la que se presentaron las conductas de desarrollo motor en el total de los niños examinados, se construyó una escala, con la cual se realizaron comparaciones, en función de género, nivel socioeconómico y calificación total en estimulación disponible en el hogar. Resultados. Los datos indican que el nivel socioeconómico alto tiene mejores calificaciones a la misma edad y género que los niños de familias de medio y bajo índice socioeconómico. Por género se observó que el femenino abandona tempranamente el gateo y presenta tardíamente la conducta de correr respecto al masculino. Por disponibilidad total de estimulación en el hogar se observó que los niños con calificación alta abandonan el gateo y presentan la conducta de correr a más temprana edad que los de baja calificación. Conclusiones. Esta escala ajustada para la población estudiada, permitió discriminar con niveles de significancia estadística el desarrollo motor en función del nivel socioeconómico del niño. Se propone el uso de esta escala como norma para la evaluación de la población infantil en el área rural mexicana. Desarrollo motor; clase socioeconómica; estimulación en el hogar; prueba de Gesell.

El ozono como molécula reactiva: concepto actual / The ozone by reactive molecule: actual concept

Los radicales libres son especies químicas de gran reactividad. El ozono se caracteriza por ser un contaminante del aire, que está presente sobre todo en las grandes ciudades, a pesar de que no es propiamente un radical libre, es promotor de varios de ellos, por ejemplo, los radicales hidroxilo y peróxido. Los radicales libres también se generan como parte del metabolismo celular y son controlados por mecanismos de carácter endógeno, principalmente de tipo enzimático, resaltan por su importancia, las enzimas superóxido dismutasa, catalasa y glutatión peroxidasa. Diversos reportes señalan la participación del ozono en la producción de alteraciones en funciones neurológicas, conductuales, endocrinas y genéticas entre otras. Por otra parte, bajo condiciones controladas, el ozono ha sido utilizado con fines terapéuticos en el tratamiento de enfermedades virales. De manera que el ozono, puede verse como benéfico o dañino, dependiendo de su concentración y de la capacidad del metabolismo celular del organismo, para regular la producción de radicales libres, hasta culminar con la oxidación de moléculas orgánicas y producir CO2 y H2O.