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.

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.

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.

Natural Steroids and Androgen Antagonists used as Neuroprotection in Common Neurological Disorders.

BACKGROUND & OBJECTIVE: Multiple classes of natural products, such as antiandrogens or steroids have been used as antioxidants and anti-inflammatory treatments in neurodegenerative diseases. This paper aims to review current knowledge on these substances and their possible relationship with free radicals as an alternative therapy and prevention of common neurological disorders. An exhaustive review of the neurochemical mechanisms of these substances in the central nervous system of humans and animal models is yet to be undertaken in the literature, particularly regarding their importance and increasing use. CONCLUSION: Androgen receptor antagonists act in a different way that may underlie the benefits of natural products, with the expectation that in adults, neurological disorders would respond to natural antiandrogens. We hope that this work would provide valuable insight into the protective and therapeutic roles for natural antiandrogens and steroids in common neurological disorders.

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.

Mechanisms involved in the development of diabetic retinopathy induced by oxidative stress.

BACKGROUND: Diabetic retinopathy (DR) is one of the main complications in patients with diabetes and has been the leading cause of visual loss since 1990. Oxidative stress is a biological process resulting from excessive production of reactive oxygen species (ROS). This process contributes to the development of many diseases and disease complications. ROS interact with various cellular components to induce cell injury. Fortunately, there is an antioxidan t system that protects organisms against ROS. Indeed, when ROS exceed antioxidant capacity, the resulting cell injury can cause diverse physiological and pathological changes that could lead to a disease like DR. OBJECTIVE: This paper reviews the possible mechanisms of common and novel biomarkers involved in the development of DR and explores how these biomarkers could be used to monitor the damage induced by oxidative stress in DR, which is a significant complication in people with diabetes. CONCLUSION: The poor control of glucemy in pacients with DB has been shown contribute to the development of complications in eyes as DR.

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.

Effect of testosterone and steroids homologues on indolamines and lipid peroxidation in rat brain.

The purpose of the present study was to evaluate the effect of 4-pregnen-17-hydroxy-3-one (A) and two steroids homologues: 3beta-acetoxy-5,16-pregnadien-20-one (B) and 3beta-acetoxy-16alpha-17alpha-epoxy-4-pregnen-20-one (C). Male Wistar rats were treated with o-cresol combined (A, B or C) steroids. Lipid peroxidation status as result of measurement reactive substances to thiobarbituric acid (TBARS) as well as serotonin (5-HT) and its precursor 5-hydroxytryptophan (5-HTP) were measured. The prostate glands were weighed, the 5alpha-reductase activity was determined. The animals treated with A, B, and C steroids showed a slight increase in both 5alpha-reductase activity and prostate size. 5-HT and 5-HTP levels did not change significantly, and TBARS showed an increase in the group treated with B steroid and a decrease in the A steroid group with significant differences in both groups (p<0.05) versus control group. Results suggest that A steroid reduces TBARS in rat brain, perhaps as a result of the interaction between the testosterone unsaturated carbons and OH(-) groups with free radicals.

Comparative effect of cyanamide and sodium nitroprusside on indolamine and lipid peroxidation levels in rat brain.

The aim of this study was to compare the effect of cyanamide (CNM) and sodium nitroprusside (SNP) on nitrite (NO2-) and nitrate (NO3-), stable metabolites of nitric oxide (NO), serotonin (5-HT), tryptophan (Trp), and lipid peroxidation (TBARS) levels in rat brain. Twenty-four male Wistar rats (350 g) were used, divided in 3 groups of 8 animals each. Control group I received 0.9 % NaCl, CNM (40 mg/kg) was administered to group II, and SNP (20 microg/kg) to group III; all animals received a single intraperitoneal dose. The animals were sacrificed by decapitation and the brain was homogenized to measure the NO2-, NO3-, 5-HT, and Trp levels by liquid chromatography, and TBARS levels by spectrophotometry. NO2- levels significantly increased (p< 0.01) in the CNM group, while 5-HT and TBARS significantly increased (p = 0.001) both in SNP and CNM groups in relation to the control group. Trp levels presented a slight increase in the CNM group with respect to the control group. The results suggest that free radicals (Nitroxyl and NO) generated by CNM and SNP, respectively, are responsible for oxidative stress induced in brain.

Antioxidant effects of selenium in rat brain and the stimulating role of nitric oxide.

OBJECTIVE: To evaluate the antioxidant effect of selenium on Na+, K(+)-ATPase in rat brain in the presence of nitric oxide. METHODS: Male Wistar rats (70 g) were treated as follows: group 1 received 1 microg of i.p. sodium nitroprus-side per kg (SNP), group 2 received 5 microg sodium selenite during 20 days, group 3 received sodium selenite 5 microg + SNP 1 microg and the control group received vehicle 50 microl (0.9% NaCl), same period and route. At the end of treatment, animals were sacrificed and their brain dissected into cortex, hemispheres, cerebellum and brain stem in order to determine lipid peroxidation (TBARS), Na+, K+ ATPase and total ATPase in each section. Blood hemoglobin concentration (Hb) and prostate weight were also assessed. RESULTS: A significant increase of Hb in blood and of proteins in cortex and hemisphere was detected, but TBARS values fell due to the effect of sodium selenite in all examined regions, except for cerebellum. ATPase activity declined in all groups and regions with and without NTP. We conclude that diet supplementary selenium to inhibit NO generation can be a useful treatment in chronic inflammatory diseases.