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.

The Use of Trace and Essential Elements in Common Clinical Disorders: Roles in Assessment of Health and Oxidative Stress Status.

During the early life, the diet of infants is mainly dominated by milk. Milk is a natural food rich in trace elements focus on essential elements. These elements are very necessary for human metabolism and since they cannot be synthesized by the body, the only source available for the humans to obtain them is by ingestion of natural food. This mini-review aims at updating the knowledge on trace elements, outlining their natural food sources, and their possible implications in common clinical disorders in early and adult life. However, it was found that consumption of food with micronutrients and trace elements may release intracellular compounds and offer oxidative protection or exacerbate oxidative damage to metabolically compromised cells.

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.

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.

Levels of glutathione and some biogenic amines in the human brain putamen after traumatic death.

Mexico City is among the world's largest metropolitan city centers and one of the most difficult and challenging cities in which to drive a motor vehicle. During peak transit hours and maximum congestion, numerous accidents occur, many of them fatal. The aim of the study presented here was to analyze the levels of select indicators against oxidative stress and levels of biogenic amines as a consequence of accident or altercation and fear deaths. Eighteen cases were studied (sixteen males, two females). Subjects ranged from twelve to eighty-one years of age. Nine of the deaths studied were the result of motor vehicle or subway accidents. Eight of the eighteen deaths were the result of a violent altercation, while one of the deaths resulted from a drug overdose and cardiac arrest. Biopsies of cadaver putamen were homogenized and analyzed for Tryptophan (Trp), 5-hydroxyindole acetic acid (5-HIAA), Dopamine (DA), and Glutathione (GSH) levels by fluorometric methods. Trp, 5-HIAA, DA, and GSH levels showed an increase in the subjects who's death was caused by violent altercation combined with fear, while DA levels showed significant differences in all accident groups. This data suggest that biogenic amines in cadaver putamen tissue, such as DA, can be telling biochemical markers, indicative of altercation and fear deaths.

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.