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

Effects of Marijuana and Diazepam on Lipid Peroxidation, Na+, K+ ATPase, and Levels of Glutathione and 5-HTP in Rat Brain

Our aim was to evaluate the effects of marijuana (Mar) and diazepam (Dz) on lipid peroxidation (TBARS), Na+, K+ ATPase activity, levels of glutathione (GSH) and 5-hydroxytryptophan (5-HTP). Male Wistar rats were given a single dose per group: extract of Mar (100 µL/kg), Dz (5 mg/kg), Mar plus Dz, and NaCl for control. Sixty mins after treatment, animals were sacrificed, and their brains extracted and homogenised to measure GSH, TBARS and 5-HTP levels. Na+, K+ ATPase and total ATPase activities. GSH and TBARS did not show differences respect to controls. Na+, K+ ATPase activity was similar as well. However, groups treated with Mar, total ATPase activity decreased significantly (p < 0.05). Levels of 5-HTP decreased significantly (p = 0.0001) in rats treated either with Mar and or Dz. Mar and Dz induced biochemical effects on the serotonergic metabolism, which can alter the development and function in rat brain, because it has also been involved in scavenging free radicals present there

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

Abstract 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 β-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 β-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 β-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

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

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

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

The Polyphenols &alpha;-Mangostin and Nordihydroguaiaretic Acid Induce Oxidative Stress, Cell Cycle Arrest, and Apoptosis in a Cellular Model of Medulloblastoma

Medulloblastoma is a common malignant brain tumor in the pediatric age. The current therapeutics present serious collateral effects. Polyphenols &alpha;-mangostin and nordihydroguaiaretic acid (NDGA) exert potent antitumoral activity in different cancer models, although their antitumoral effects have not been described in medulloblastoma cells yet. This study aimed to examine the proapoptotic effects of these polyphenols on human medulloblastoma cells. Medulloblastoma cell line Daoy was incubated with increasing concentrations of &alpha;-mangostin or NDGA for 24 h. The cell viability was analyzed using crystal violet and trypan blue dyes. Determination of the glutathione (GSH)/glutathione disulfide (GSSG) ratio and levels of carbonylated proteins was performed to evaluate the oxidative stress. Cell cycle progression and induction of cell death by fluorochrome-couple and TUNEL assays were evaluated using flow cytometry assays. Individual treatments with &alpha;-mangostin or NDGA decreased the viability of Daoy cells in a dose-dependent manner, inducing G2/M and S-G2/M cell cycle arrest, respectively. Both polyphenols induced cell death and increased oxidative stress. Very interestingly, &alpha;-mangostin showed more potent effects than NDGA. Our results indicate that &alpha;-mangostin and NDGA exert important cytostatic and cytotoxic effects in the Daoy cell line. These data highlight the potential usefulness of these compounds as an alternative strategy in medulloblastoma treatment