Assessment of the Roles of Magnesium and Zinc in Clinical Disorders.

The ability and facility of magnesium (Mg2+) and zinc (Zn2+) to interact with phosphate ions confer them the characteristics of essential trace elements. Trace elements are extremely necessary for the basic nucleic acid chemistry of cells of all known living organisms. More than 300 enzymes require zinc and magnesium ions for their catalytic actions, including all the enzymes involved in the synthesis of ATP. In addition, enzymes such as isomerases, oxidoreductases, lyases, transferases, ligases and hydrolases that use other nucleotides to synthesize DNA and RNA require magnesium and zinc. These nucleotides may trigger oxidative damage or important changes against free radicals. In the same way, nucleotides may play an important role in the pathophysiology of degenerative diseases, including in some clinical disorders, where vascular risk factors, oxidative stress and inflammation work to destabilize the patients` homeostatic equilibrium. Indeed, reduced levels of zinc and magnesium may lead to inadequate amount of antioxidant enzymes, and thus, acts as an important contributing factor for the induction of oxidative stress leading to cellular or tissue dysfunction. Hence, the development of zinc or magnesium enzyme inhibitors could be a novel opportunity for the treatment of some human disorders. Therefore, the objective of the present work was to assess the clinical benefits of zinc and magnesium in human health and their effects in some clinical disorders.

Inflammatory Process and Immune System in Major Depressive Disorder.

Major depressive disorder (MDD) is one of the most common psychiatric illnesses in the general population. In mental disorders, the activation of inflammatory pathways in the brain is a major producer of excitotoxicity and an inducer of oxidative stress. The occurrence of these 2 events is partly responsible for the neuronal damage inherent in patients with mental disorders. In the case of MDD, the release of hormone and increase in pro-inflammatory cytokines in plasma and indicators of oxidative stress have been identified as consequences of this event. The most important affectations in patients with MDD are changes in their cognitive and executive functions due to brain inflammation. Hence, these biomarkers can serve as diagnostic and severity classification tools and treatment. In this work, we described the communication pathway between the immune and neuroendocrine systems in MDD and suggested possible therapeutic options for the disease.

Sildenafil alters biogenic amines and increases oxidative damage in brain regions of insulin-hypoglycemic rats.

The aim of the present study was to determine the effect of sildenafil on dopamine, 5-hydroxyindol acetic acid (5-HIAA) and selected biomarkers of oxidative stress in the brain of hypoglycemic rats. The animals were treated intraperitoneally as follows: group 1 (control), saline solution; group 2, insulin (10 U per rat or 50 U kg-1); group 3, insulin + single dose of sildenafil (50 U kg-1 + 50 mg kg-1); group 4, insulin + three doses of sildenafil every 24 hours (50 U kg-1 + 50 mg kg-1). In groups 2, 3 and 4, insulin was administered every 24 hours for 10 days. Blood glucose was measured after the last treatment. On the last day of the treatment, the animals´ brains were extracted to measure the levels of oxidative stress markers [H2O2, Ca2+,Mg2+-ATPase, glutathione and lipid peroxidation (TBARS)], dopamine and 5-HIAA in the cortex, striatum and cerebellum/medulla oblongata by validated methods. The results suggest that administration of insulin in combination with sildenafil induces hypoglycemia and hypotension, enhances oxidative damage and provokes changes in the brain metabolism of biogenic amines. Administration of insulin and sildenafil promotes biometabolic responses in glucose control, namely, it induces hypoglycemia and hypotension. It also enhances oxidative damage and provokes changes in the brain metabolism of biogenic amines.

Insulin plus zinc induces a favorable biochemical response effects on oxidative damage and dopamine levels in rat brain.

The aim was to determine the effect of zinc (Zn) and insulin on oxidative stress and levels of dopamine in brain of rats. Wistar rats were treated either with zinc alone or combined with insulin during 10 days. After the last dose blood glucose was measured. Their brains were extracted to measure H2O2, Ca+2, Mg+2 ATPase, glutathione (GSH), lipid peroxidation (Tbars) and Dopamine. Zn does not possess anti-glycemic effect like Insulin however, it is noticeable that the combination of Insulin plus Zn induces a major glucose reduction (p < 0.0001) than Insulin alone. In cerebellum/medulla oblongata, the groups treated with Insulin and Zn show a significantly increase in dopamine (p < 0.005). Insulin plus Zn reduced GSH level in cortex. Insulin plus Zn reduced level of H2O2 in Striatum and in cerebellum/medulla oblongata. Lipid peroxidation was significantly reduced by the administration of Insulin as in the combination of Insulin and Zn in all regions (p < 0.0001). In cerebellum medulla oblongata, ATPase activity showed an increase only in the group treated with Insulin + Zn. CONCLUSION: These results suggest that the use of insulin plus Zn produce favorable changes on oxidative stress and this as consequence on the levels of dopamine.

Cytarabine and Ferric Carboxymaltose (Fe+3) Increase Oxidative Damage and Alter Serotonergic Metabolism in Brain.

BACKGROUND & OBJECTIVE: The purpose of this study was to measure the effect on brain biomarkers after treatment with anticancer compounds - cytarabine (CT) and ferric carboxymaltose (FC) (Fe+3) in Wistar rats. METHODS: The Wistar rats were treated as follows: group 1 (control), NaCl 0.9%; group 2, CT (25 mg/k), group 3, FC(Fe+3) (50 mg/k) and group 4, CT + FC(Fe+3). The animals were sacrificed and their brains were obtained and used to measure lipoperoxidation (TBARS), H2O2, Na+, K+ ATPase, glutathione (GSH), serotonin metabolite (5-HIAA) and dopamine. The results indicated an enhancement of lipid peroxidation in the cortex and striatum of groups treated with FC(Fe+3) and CT, while GSH decreased in the cortex of group treated with CT + FC(Fe+3). Dopamine decreased in the cortex of the rats that received CT, while in the striatum, 5HIAA increased in all groups. RESULTS & CONCLUSION: These results suggest that the treatment with CT and FC(Fe+3) boosted oxidative stress and led to an alteration in momoamine concentrations in the brain.

Riboflavin and pyridoxine restore dopamine levels and reduce oxidative stress in brain of rats.

BACKGROUND: Neurological disorders suggest that the excitotoxicity involves a drastic increase in intracellular Ca2+ concentrations and the formation of reactive oxygen species. The presence of these free radicals may also affect the dopaminergic system. The aim of this work was to determine if riboflavin (B2) and pyridoxine (B6) provide protection to the brain against free radicals generated by 3-nitropropionic acid (3-NPA) by measuring the levels of dopamine (DA) and selected oxidative stress markers. METHODS: Male Fisher rats were grouped (n = 6) and treated as follows: group 1, control (NaCl 0.9%); group 2, 3-NPA (20 mg/kg); group 3, B2 (10 mg/kg); group 4, B2 (10 mg/kg) + 3-NPA (20 mg/kg); group 5, B6 (10 mg/kg) and group 6, B6 + 3-NPA. All treatments were administered every 24 h for 5 days by intraperitoneal route. After sacrifice, the brain was obtained to measure DA, GSH, and lipid peroxidation, Ca2+, Mg2+, ATPase and H2O2. MAIN FINDINGS: Levels of dopamine increased in cortex, striatum and cerebellum/medulla oblongata of animals that received 3-NPA alone. The lipid peroxidation increased in cortex, striatum, and cerebellum/medulla oblongata, of animals treated with B2 vitamin alone. ATPase dependent on Ca+2, Mg+2 and H2O2 increased in all regions of animals that received 3-NPA alone. CONCLUSION: The results confirm the capacity of 3-NPA to generate oxidative stress. Besides, the study suggests that B2 or B6 vitamins restored the levels of DA and reduced oxidative stress in brain of rats. We believe that these results would help in the study of neurodegenerative diseases.

ß-Cyclodextrin and oleic acid increase levels of dopamine and potentiates oxidative damage in young and adult rat brain.

BACKGROUND: Cyclodextrins are active pharmaceutical ingredients to treat neurological diseases by reducing neurotoxicity. The aim of this study was to test if combined consumption of ß-cyclodextrin (BCD) and Oleic acid (OA) potentiates brain antioxidant protection. METHODS: Four groups of young Wistar rats, grouped in 6 animals each, were treated as follows: Group (G) 1, saline solution 0.9% (control); G2, BCD (0.7 g/kg); G3, OA (15 ml/kg); G4, BCD + OA. The same design was assayed for groups of adult rats. Treatments were daily administered by oral means for five consecutive days. On the last day of administration, brains of the animals were extracted to measure dopamine, 5-HIAA, glutathione (GSH), ATPase, Lipoperoxidation and H2O2. RESULTS: Oleic acid and ß-cyclodextrin upgraded the levels of dopamine, 5-HIAA and lipid peroxidation and downgraded the concentrations of GSH and H2O2 in cortex, hemispheres (striatum) and cerebellum/medulla oblongata regions. CONCLUSIONS: The results of the present study suggest that combined use of oleic acid and ß-cyclodextrin may increase oxidative damage in brain regions and promote alteration in dopamine and 5-HIAA amines and hence, constitutes health risks among age of subjects.

Biochemical and histological changes produced by sweeteners and cytarabine in the brain of young rats / Cambios bioquímicos e histológicos producidos por edulcorantes y citarabina en el cerebro de ratas jóvenes

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)

Oseltamivir and indomethacin reduce the oxidative stress in brain and stomach of infected rats.

The aim of this study was to determine the effect of oseltamivir and indomethacin on lipid peroxidation (LP), GABA levels, and ATPase activity in brain and stomach of normal and infected rats (IR), as novel inflammation model. Female Sprague Dawley rats grouped five each, either in the absence or presence of a live culture of Salmonella typhimurium (S. typh), were treated as follows: group 1 (control), PBS buffer; group 2, oseltamivir (100 mg/kg); group 3, indomethacin (67 µg/rat); group 4, oseltamivir (100 mg/kg) + indomethacin (67 µg/rat). All drugs were given intraperitoneally for 5 days. IR received the same treatments and the brain and stomach of the rats were removed in order to measure levels of GABA, LP, and total ATPase, using validated methods. Levels of GABA increased in stomach and cortex of IR with oseltamivir, but decreased in striatum and cerebellum/medulla oblongata of IR with indomethacin. LP decreased in the three brain regions of IR with oseltamivir. ATPase increased in stomach of IR and non-IR with oseltamivir and in striatum and cerebellum/medulla oblongata of IR with indomethacin. Results suggest that the effect of free radicals produced in an infection and inflammatory condition caused by S. typh could be less toxic by a combination of oseltamivir and indomethacin.

Trace elements cause oxidative damage in the brain of rats with induced hypotension.

Hypertension causes neuronal damage and apoptosis in the brain. Diazoxide is a drug used in the treatment of hypertension however, its effect on 5-hydroxyindole acetic acid (5-HIAA) and dopamine amines in adult animal models remains unclear. The purpose of this study was to determine the effect of oligoelements on 5-HIAA and dopamine in the brain of adult rats treated with diazoxide METHODS: Male Fisher rats (weight 250g) were treated as follows: Group I, NaCl 0.9% (control); group II, tracefusin® (1.5mL/rat); group III, diazoxide (20mg/rat) and group IV, tracefusin® (1.5mL/rat)+diazoxide (20mg/rat). All doses were intraperitoneally administered on daily basis for four consecutive days. After the last administration, the brain of the animals was obtained and dissected in cortex, hemispheres (striatum) and cerebellum/medulla oblongata to measure the levels of 5-HIAA, dopamine, lipid peroxidation and total ATPase activity through validated methods. RESULTS: Dopamine and 5-HIAA levels decreased significantly in the group that received trace elements and diazoxide in the hemisphere regions, while in cerebellum/medulla oblongata, dopamine levels increased significantly in the groups that received diazoxide alone in. Lipid peroxidation in all brain regions increased significantly in the groups that received trace elements and diazoxide. ATPase dependent of calcium and magnesium decreased in the groups that received diazoxide alone or combined with trace elements in cerebellum/medulla oblongata regions. CONCLUSION: The present results suggest that the use of trace elements and diazoxide alters metabolism of dopamine and 5-HIAA amines. Free radicals may be involved in this effect.

Assessment of Mexican Arnica (Heterotheca inuloides Cass) and Rosemary (Rosmarinus officinalis) Extracts on Dopamine and Selected Biomarkers of Oxidative Stress in Stomach and Brain of Salmonella typhimurium Infected rats.

BACKGROUND: The effects of some natural products on dopamine (DA) and 5-hydroxyindole acetic acid (5-HIAA) in brain of infected models are still unclear. OBJECTIVE: The purpose of this study was to measure the effect of Mexican arnica/rosemary (MAR) water extract and oseltamivir on both biogenic amines and some oxidative biomarkers in the brain and stomach of young rats under infection condition. METHODS: Female Wistar rats (weight 80 g) in the presence of MAR or absence (no-MAR) were treated as follows: group 1, buffer solution (controls); oseltamivir (100 mg/kg), group 2; culture of Salmonella typhimurium (S.Typh) (1 × 106 colony-forming units/rat) group 3; oseltamivir (100 mg/kg) + S.Typh (same dose) group 4. Drug and extracts were administered intraperitoneally every 24 h for 5 days, and S.Typh was given orally on days 1 and 3. On the fifth day, blood was collected to measure glucose and hemoglobin. The brains and stomachs were obtained to measure levels of DA, 5-HIAA, glutathione (GSH), TBARS, H2O2, and total ATPase activity using validated methods. RESULTS: DA levels increased in MAR group treated with oseltamivir alone but decreased in no-MAR group treated with oseltamivir plus S.Typh. 5-HIAA, GSH, and H2O2 decreased in this last group, and ATPase activity increased in MAR group treated with oseltamivir plus S.Typh. TBARS (lipid peroxidation) increased in MAR group that received oseltamivir alone. Most of the biomarkers were not altered significantly in the stomach. CONCLUSION: MAR extract alters DA and metabolism of 5-HIAA in the brain of young animals infected. Antioxidant capacity may be involved in these effects. SUMMARY: The purpose of this study was to measure the effect of Mexican arnica/rosemary water extract and oseltamivir on both biogenic amines and some oxidative biomarkers in the brain and stomach of young rats under infection condition. Results: Mexican arnica and rosemary extract alter dopamine and metabolism of 5-HIAA in the brain of young animals infected. Antioxidant capacity may be involved in these effects. Abbreviations used: AS: Automated system, ATP: Adenosine triphosphate, CNS: Central nervous system, CFU: Colony-forming unit, DA: Dopamine EDTA: Ethylenediaminetetraacetic acid, 5-HIAA: Äcido 5-hidroxindolacético (serotonina), GABA: γ-aminobutyric acid, GSH: Glutathione, H2O2: Hidrogen peroxide, HCLO4: Perchloric acid, iNOS: Inducible nitric oxide synthase, LPS: Lipopolysaccharides, MAR: Arnica/Rosemary, NaCl: Sodium Chloride, NOGSH: nitrosoglutathione, NOS: Nitric oxide, OPT: Ortho-phtaldialdehyde, Pbs: Phosphate buffered saline, pH: potential of Hydrogen, Pi: Inorganic phosphate, ROS: Reactive oxygen species, RNSs: Reactive nitrogen species Tba: Thiobarbaturic acid, TBARS: Thiobarbituric aid reactive, Tca: Trichloroacetic, Tris-HCL: Tris hydrochloride, TSA: Trypticasein Soya Agar.

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.

Assessment of the effects of oseltamivir and indomethacin on dopamine, 5-HIAA, and some oxidative stress markers in stomach and brain of Salmonella typhimurium-infected rats.

OBJECTIVES: The purpose of this study was to measure the effect of oseltamivir and indomethacin on dopamine and 5-HIAA levels and some oxidative biomarkers in brain and stomach of young rats in conditions of infection. METHODS: Female Sprague Dawley rats in absence or presence of a live culture of Salmonella typhimurium (S.Typh), were treated as follows: PBS, group 1 (control); oseltamivir (100 mg/kg), group 2; indomethacin (67 µg/kg) group 3; oseltamivir (100 mg/kg) + indomethacin (67 µg/kg), group 4. The drugs were administered intraperitoneally every 24 hr for 5 days while S. Typh was give orally in the first and third day. C-reactive proteins was measured in blood on sacrifice, and from brain extract, dopamine and 5-HIAA levels as well as GSH, calcium, and H2O2 and total ATPase activity were measured by validated methods. RESULTS: Dopamine increased significantly in cortex and cerebellum/medulla oblongata of groups that received indomethacin and oseltamivir. 5-HIAA increased significantly in all groups that received S.Typh. H2O2 decreased significantly in cortex regions of animals that received oseltamivir and indomethacin in presence of S.Typh. Total ATPase increased significantly in cortex and hemispheres of groups that received oseltamivir as well as in cerebellum/medulla oblongata and stomach of animals that received oseltamivir and indomethacin combined with S.Typh. GSH increased and calcium decreased significantly in stomach of animals that received oseltamivir or indomethacin alone or combined with S.Typh. CONCLUSION: These results demonstrate the association between inflammatory response, oxidative stress, dopaminergic, and serotonergic metabolism in an experimental inflammatory animal model.

Oleic Acid Protects Against Oxidative Stress Exacerbated by Cytarabine and Doxorubicin in Rat Brain.

AIM: The objective of this study was to analyze the effect of doxorubicin and cytarabine on biogenic amines and oxidative biomarkers in the brain of rats treated with oleic acid. METHODS: Thirty-six Wistar rats distributed in 6 groups, were treated as follows: group 1 (control), NaCl 0.9%; group 2 doxorubicin (1mg/kg); group 3 cytarabine (70mg /kg); group 4 oleic acid (1500µl/kg); group 5 doxorubicin + oleic acid; group 6 cytarabine + oleic acid. All compounds were administered intraperitoneally for 5 days. The Rats were sacrificed after receiving the last administration and their brains were dissected in cortex, hemispheres, and cerebellum/medulla oblongata. Blood samples were obtained on sacrifice to assess the levels of glucose and triglycerides. In each brain region, lipoperoxidation (TBARS), H2O2, Na+, K+ ATPase, glutathione (GSH), serotonin metabolites (5-HIAA) and dopamine were measured using validated methods. RESULTS: Cytarabine decreased the levels of dopamine, TBARS, GSH, H2O2 and ATPase in all regions. Doxorubicin combined with oleic acid increased the levels of GSH in cortex, and decreased ATPase in cerebellum/medulla oblongata. CONCLUSION: These results suggest that the reduction of dopamine and oxidant effect during cytarabine treatment could result in brain injury but could be prevented by oleic acid supplementation.

Moieties in antidiabetic drugs as a target of insulin receptors in association with common neurological disorders.

Insulin is a peptide that can be harmful with regards to neuroplasticity, neuroprotection and neuromodulation. Furthermore, the role of insulin highlights its relevance in the progress of diverse clinical disorders as well as in the mechanisms associated with certain pathogenesis and their evolution towards diabetes, obesity and neurodegenerative diseases. The precise molecular mechanisms by which these diseases are induced remain to be elucidated. The benefits in knowing/discovering these mechanisms in animal models and humans cannot be undermined. An in depth understanding of the principal risk factors leading to obesity and their management is vital in the implementation of early-life strategies of intervention and prevention, with a view to avoid adverse late-life outcomes. Therefore, the aim of the present study was to review their possible association with antidiabetic drugs.

Effect of two antiandrogens as protectors of prostate and brain in a Huntington's animal model.

The purpose of this work is to know the effect of flutamide and a novel synthetic steroid 3ß-p-Iodobenzoyloxypregnan-4,16- diene-6,20-dione (IBP) on the levels of dopamine, 5-HIAA (5-hydroxyindole acetic acid), and some oxidative stress markers in animal model with Huntington disease. Thirty male Wistar rats divided in groups of 6 animals each were subjected to the following treatment: group A, 3-nitro propionic acid (3-NPA, as inducer of Huntington); group B, flutamide; group C, 3-NPA + flutamide; group D, IBP; and group E, 3-NPA + IBP. Treatment scheme for all groups were at 4 mg/kg/day administered intraperitoneally. The measurement of haemoglobin was carried out from blood while the concentrations of ATPase, 5α-reductase, reduced glutathione (GSH), calcium, H2O2, 5-HIAA, and dopamine were determined from brain and prostate tissues using validated methods. The results depicted a significant decrease of dopamine and GSH in cerebellum/Medulla oblongata of animals treated with IBP. The prostate gland of the same group of treatment also showed a significant decrease in the concentrations of TBARS, H2O2, and total ATPase. In hemispheres of groups D and E, dopamine, H2O2, and total ATPase decreased significantly while in prostate, hemispheres, and cerebellum/Medulla oblongata of groups B and C; calcium, 5α-reductase, ATPase, H2O2, and TBARS were found to witness a significant decrease. Results showed an antiandrogenic activity of flutamide, while the novel steroid IBP showed neuroprotective properties by changes on oxidative stress biomarkers as critical pathways leading to prostate and brain degeneration. Probably steroid homeostasis disequilibrium could have led to alterations in dopamine metabolism GSH in Huntington's disease animal models.

Effect of oseltamivir on catecholamines and select oxidative stress markers in the presence of oligoelements in the rat brain.

The effect that osteltamivir has on the metabolism of catecholamines and oxidative damage in the brains of young patients remains unclear. The purpose of this study was to measure the effects of oseltamivir, in the presence of oligoelements, on biogenic amines and select oxidative biomarkers in the brains of uninfected, young rats under normal conditions. The study was conducted using male Wistar rats intraperitoneally treated for three days with either a control dose of 0.9 % NaCl, oseltamivir (50 mg/kg), oligoelements (50 µL/rat), or oseltamivir (50 mg/kg) and oligoelements (50 µL/rat). The brain tissue extracted from the treated rats was used to determine the concentrations of adrenaline, noradrenaline, and dopamine, as well as the levels of GSH, lipid peroxidation, and ATPase activity. An increase in the concentration of adrenaline and noradrenaline and in the level of GSH in the group treated with oligoelements (p < 0.001) was observed, while the group treated with oseltamivir and oligoelements, the levels of dopamine increased (p < 0.001), and in the groups treated with oligoelements alone or combination with oseltamivir a decrease in lipid peroxidation was observed (p < 0.001). The results of this study suggest that the consumption of oseltamivir and oligoelements induce biphasic changes in the metabolism of catecholamines; thereby, inducing a protective mechanism against oxidative damage in the brains of young rats.

Cerebrolysin and morphine decrease glutathione and 5-hydroxyindole acetic acid levels in fasted rat brain.

PURPOSE: The aim was to evaluate if morphine sulphate combined with cerebrolysin enhances the risk of oxidative damage in the presence of moderate hypoglycaemia. METHODS: Wistar rats under starvation for 48h received a single dose of 215 mg/kg cerebrolysin or 4 mg/kg morphine sulphate. Glutathione (GSH) and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured in brain tissue, as well as lipid peroxidation, Na(+)-K(+) ATPase and total ATPase enzymatic activities, by fluorescence and spectrophotometric methods. RESULTS: GSH and 5-HIAA levels decreased significantly (p<0.05) in animals which received cerebrolysin and morphine alone or combined. TBARS levels increased in all groups, but the values were statistically significant only in those animals that received cerebrolysin combined with morphine (p<0.05). Na(+)-K(+) ATPase and total ATPase activities decreased significantly in rats treated only with morphine, but the cerebrolysin and morphine groups showed a significant increase in these enzymatic activities. CONCLUSIONS: Results suggest that cerebrolysin as well as morphine induced changes in cellular regulation and biochemical responses to oxidative stress induced by moderate hypoglycaemia in brain.

Assessment of oxidative damage induced by acute doses of morphine sulfate in postnatal and adult rat brain.

The aim of the present study is to evaluate the oxidative damage in rats of different ages. Weaned rats of 25 g and adults of 300 g were used in groups of 6, a single i.p. dose of morphine sulfate of 3, 6 or 12 mg/kg was administered. All animals were sacrificed to measure GSH and 5-HT levels in brain by liquid chromatography, as well as Na(+), K(+)-ATPase and total ATPase enzymatic activity. 5-HT levels decreased significantly (p < 0.05) in adult animals that received 3 and 6 mg morphine. Na(+), K(+)-ATPase activity increased significantly (p < 0.05) in all groups of weaned animals. In adult animals, Na(+), K(+)-ATPase and total ATPase partially diminished. GSH levels diminished significantly (p < 0.05) both in weaned and in adult groups. The results indicate age-induced changes in cellular regulation and biochemical responses to oxidative stress induced by morphine.