ATPase Activity In Brain Research Articles

Senolytics prevent age-associated changes in female mice brain

PurposeConsidering that the combination of dasatinib and quercetin (D + Q) demonstrated a neuroprotective action, as well as that females experience a decline in hormonal levels during aging and this is linked to increased susceptibility to Alzheimer’s disease, in this study we evaluated the effect of D + Q on inflammatory and oxidative stress markers and on acetylcholinesterase and Na+, K+-ATPase activities in brain of female mice. MethodsFemale C57BL/6 mice were divided in Control and D (5 mg/kg) + Q (50 mg/kg) treated. Treatment was administered via gavage for three consecutive days every two weeks starting at 30 days of age. The animals were euthanized at 6 months of age and at 14 months of age. ResultsResults indicate an increase in reactive species (RS), thiol content and lipid peroxidation followed by a reduction in nitrite levels and superoxide dismutase, catalase and glutathione S-transferase activity in the brain of control animals with age. D+Q protected against age-associated increase in RS and catalase activity reduction. Acetylcholinesterase activity was increased, while Na+, K+-ATPase activity was reduced at 14 months of age and D+Q prevented this reduction. ConclusionThese data demonstrate that D+Q can protect against age-associated neurochemical alterations in the female brain.

Sub‑chronic administration of lead alters markers of oxidative stress, acetylcholinesterase and Na+K+‑ATPase activities in rat brain.

This study investigated the effects of sub‑chronic administration of lead (Pb) acetate on thiobarbituric acid reactive substances (TBA‑RS), total sulfhydryl content, protein carbonyl content, antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GSH‑Px]), acetylcholinesterase (AChE), and Na+K+‑ATPase in the cerebral structures of rats. Male Wistar rats aged 60 days were treated with saline (control group) or Pb (treatment group), at various doses, by gavage, once a day for 35 days. The animals were sacrificed twelve hours after the last administration, and the cerebellum, hippocampus and cerebral cortex were removed. The results showed that Pb did not alter the evaluated oxidative stress parameters. Furthermore, Pb (64 and/or 128 mg/kg) altered SOD in the cerebellum, cerebral cortex and hippocampus. Pb (128 mg/kg) altered CAT in the cerebellum and cerebral cortex and GSH‑Px in the cerebral cortex. Also, Pb (64 mg/kg and 128 mg/kg) altered GSH‑Px in the cerebellum. Moreover, Pb (128 mg/kg) increased AChE in the hippocampus and decreased Na+K+‑ATPase in the cerebellum and hippocampus. In conclusion, sub‑chronic exposure to Pb (occupational and environmental intoxication) altered antioxidant enzymes, AChE, and Na+K+‑ATPase, contributing to cerebral dysfunction.

New insights into arsenic, lead, and iron neurotoxicity: Activation of MAPK signaling pathway and oxidative stress.

Toxic metals cause neurodegeneration via formation of toxic complexes with the cellular compounds and production of highly reactive oxygen species. The present study aimed to investigate the role of mitogen-activated protein kinase (MAPK) signaling pathway in iron, lead, and arsenic induced neurotoxicity. Also, to explore their effect on brain enzymes, inducible nitric oxide synthase (iNOS) and nuclear factor κB (NF-κB) in rat brains. Rats were divided into four groups (n = 8): Control group, lead group (30 mg/kg lead acetate), arsenic group (5 mg/kg sodium arsenite), and iron group (100 mg/kg ferric hydroxide). Treatments were given three times/week orally for 2 months. Brain tissues were assessed for reduced glutathione and malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), alkaline phosphatase (ALP), acid phosphatase (ACP), Na+ /K+ activated adenosine 5'-triphosphatase (Na+ /K+ -ATPase)and acetylcholinesterase (AChE) activities, expression of iNOS and NF-κB, and Western blot analysis of c-Jun NH(2)-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK) proteins. Levels of arsenic, iron, and lead were significantly (p = 0.000) increased in blood and brain tissues. Levels of MDA, SOD, CAT, iNOS, and NF-κB gene expression, phosphorylated JNK and phosphorylated ERK proteins were increased significantly in lead, arsenic, and iron treated rat groups compared to control. ALP, ACP, AChE, and ATPase activities in brain were significantly altered in metal-treated rat groups compared to control. Iron, lead, and arsenic induced neurotoxicity activated the pro-inflammatory mediators NF-κB, iNOS, and MAPK pathway and altered the activity of brain ALP, ACP, Na+ /K+ -ATPase, CAT, SOD, and AChE.

Gold Compounds Inhibit the Ca2+-ATPase Activity of Brain PMCA and Human Neuroblastoma SH-SY5Y Cells and Decrease Cell Viability

Plasma membrane calcium ATPases (PMCA) are key proteins in the maintenance of calcium (Ca2+) homeostasis. Dysregulation of PMCA function is associated with several human pathologies, including neurodegenerative diseases, and, therefore, these proteins are potential drug targets to counteract those diseases. Gold compounds, namely of Au(I), are well-known for their therapeutic use in rheumatoid arthritis and other diseases for centuries. Herein, we report the ability of dichloro(2-pyridinecarboxylate)gold(III) (1), chlorotrimethylphosphinegold(I) (2), 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidenegold(I) chloride (3), and chlorotriphenylphosphinegold(I) (4) compounds to interfere with the Ca2+-ATPase activity of pig brain purified PMCA and with membranes from SH-SY5Y neuroblastoma cell cultures. The Au(III) compound (1) inhibits PMCA activity with the IC50 value of 4.9 µM, while Au(I) compounds (2, 3, and 4) inhibit the protein activity with IC50 values of 2.8, 21, and 0.9 µM, respectively. Regarding the native substrate MgATP, gold compounds 1 and 4 showed a non-competitive type of inhibition, whereas compounds 2 and 3 showed a mixed type of inhibition. All gold complexes showed cytotoxic effects on human neuroblastoma SH-SY5Y cells, although compounds 1 and 3 were more cytotoxic than compounds 2 and 4. In summary, this work shows that both Au (I and III) compounds are high-affinity inhibitors of the Ca2+-ATPase activity in purified PMCA fractions and in membranes from SH-SY5Y human neuroblastoma cells. Additionally, they exert strong cytotoxic effects.

Oral Exposure to Tributyltin Induced Behavioral Abnormality and Oxidative Stress in the Eyes and Brains of Juvenile Japanese Medaka (Oryzias latipes).

The widely used compound tributyltin (TBT), which can be continuously detected in aquatic species and seafood, may induce diverse adverse effects on aquatic organisms. However, little is known regarding the mechanistic links between behavioral abnormality and oxidative stress in different fish tissues in response to oral TBT exposure. Herein, juvenile Japanese medaka (Oryzias latipes) were orally exposed to TBT at 1 and 10 ng/g-bw/d for four weeks. After exposure, the locomotor activity and social interaction of juvenile medaka were found to be significantly reduced in the 10 ng/g-bw/d TBT-exposed group. Furthermore, the antioxidant biomarkers in different tissues of juvenile medaka showed different levels of sensitivity to TBT exposure. The eye superoxide dismutase (SOD) activities markedly increased in both groups exposed to 1 and 10 ng/g-bw/d TBT, while the eye and brain malondialdehyde (MDA) levels increased in the higher dose group. Furthermore, the eye and brain ATPase activities markedly declined in the 1 ng/g-bw/d TBT-exposed group. A correlation analysis revealed that the decreased locomotor activity and social interaction in medaka were associated with the eye antioxidant enzyme (i.e., SOD and catalase (CAT)) activity and brain oxidative damage level. Thus, our findings suggested that there might be some mechanistic links between the behavioral abnormality induced by TBT exposure and oxidative stress in the eyes and brains of medaka. Thus, our findings indicate that the impacts of oral exposure to TBT should be considered to better assess its risk to the aquatic ecosystem and human health.

Effect of Autranellacongolensis on Lipid Profile of Rats’ Brain with Experimentally Induced Alzheimer’s Disease

Lipids are essentials components of the brain. Changes in brain lipid composition affect the physical and functional properties of the neuronal cell membrane and have been implicated in the physiopathology of Alzheimer disease (AD). We evaluated in this study the effect of hydroethanolicbark extract of A. Congolensis on lipid profile of rats’ brain with experimentally induced AD. The experimental model consisted of female rats, which received orally for 8 consecutive weeks a single dose of 50 mg/Kg b.w./day of aluminum trichloride (AlCl3) (except control group) followed by distilled water (disease control group) or doses of the extract (150 or 300 mg/Kg b.w./day) or vitamin E (100 mg/Kg b.w./day) or galanthamine (2 mg/Kg b.w. /day). Brain cholesterol, phospholipids and plasmalogenlevels and fluidity were evaluated. Brain membranes ATPase activities, Ca2+, Mg2+and glucose levels were also assayed. Significant modifications of brain lipid composition and fluidity were observed in disease control group compared with control. In addition, Na+, K+-ATPase and Mg2+-ATPase activities significantly decreased, the level of intracellular Ca2+ increased, Mg2+ content decreased and brain glucose level was significantly higher. Standard drugs (vitamin E,galanthamine) showed a negative effect on brain lipid profile. The extract of 150 mg showed significant improvements of brain lipid profile and fluidity. It also indicated improved brain ATPase activities, ions and glucose brain homeostasis. The extract (150 mg/Kg b.w. dose) by maintaining the brain lipid composition may protect neuronal cell membraneand probably preventing the progression of AD.

ECMO attenuates inflammation response and increases ATPase activity in brain of swine model with cardiac arrest compared with CCPR.

Extracorporeal membrane oxygenation (ECMO) could increase survival rate and neurological outcomes of cardiac arrest (CA) patients compared with conventional cardiopulmonary resuscitation (CCPR). Currently, the underlying mechanisms how ECMO improves neurological outcomes of CA patients compared with CCPR have not been revealed. A pig model of CA was established by ventricular fibrillation induction and then underwent CCPR or ECMO. Survival and hemodynamics during the 6 h after return of spontaneous circulation (ROSC) were compared. The levels of inflammatory cytokines and Ca2+-ATPase and NA+-K+-ATPase activities were detected. Brain tissues histology and ultra-microstructure in CCPR and ECMO groups were also examined. Results suggested that ECMO significantly improved the survival of pigs compared with CCPR. Heart rate (HR) decreased while cardiac output (CO) increased along with the time after ROSC in both ECMO and CCPR groups. At each time point, HR in ECMO groups was lower than that in CCPR group while CO and mean arterial pressure in ECMO group was higher than CCPR group. In ECMO group, lower levels of IL-1, IL-1β, IL-6, TNFα, and TGFβ, especially IL-1, IL-6, TNFα, and TGFβ, were found compared that in CCPR group while no difference of IL-10 between the two groups was observed. Similar with the results from enzyme-linked immunosorbent assay, decreased expressions of IL-6 and TGFβ were also identified by Western blotting. And Ca2+-ATPase and NA+-K+-ATPase activities were increased by ECMO compared with CCPR. Hematoxylin and eosin staining and ultra-microstructure examination also revealed an improved inflammation situation in ECMO group compared with CCPR group.

Neuroprotective potential of Cucurbita maxima Duchesne ex Poir, Caeselpenia bunduc (L.) Roxb and Bombax ceiba Linn extracts

Plant derived molecules are gaining importance as an alternative to synthetic drugs for the treatment of cognitive and related disorders. Modulation of cholinesterases, monoamine oxidases and sodium–potassium ATPase activities in brain through phyto-molecules has been found effective in the treatment and management of cognitive disorders. Considering the pleiotropic action of plant secondary metabolites, the present investigation was undertaken to explore neuroprotective activity of the ethanolic and hexane extracts from Cucurbita maxima Duchesne ex Poir (seeds), Caeselpenia bunduc (L.) Roxb (seeds) and Bombax ceiba Linn (flowers). To investigate the neuroprotective activity of these plant extracts, cholinesterases (acetylcholinesterase and butyrylcholinesterase), monoamine oxidase (MAO) and Na+/K+ ATPase activities were estimated. To test if chosen plant extracts have also effect on oxidative stress lipid peroxidation and metal chelating ability were determined in mice brain homogenate. In this investigation the ethanolic and hexane extracts from these plants were able to inhibit the acetylcholinesterase and butyrylcholinesterase (43.32–69.94%), which was comparable to standard drug, donepezil at the concentration of 50 μg/ml. The chromatographic (HPTLC) estimation revealed the maximum presence of quercetin in C. maxima whereas p-coumaric acid and gallic acid were found as major constituents in B. ceiba. In conclusion, the findings of current study provide evidence for the selected plant extracts with potent cholinesterase activity which can be taken as lead for further mechanistic study and also for development of plant based formulation after pre-clinical evaluation.

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 (100mg/kg); group 3, indomethacin (67μg/rat); group 4, oseltamivir (100mg/kg)+indomethacin (67μg/rat). All drugs were given intraperitoneally for 5days. 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.

Hypoxia acclimation protects against oxidative damage and changes in prolactin and somatolactin expression in silver catfish (Rhamdia quelen) exposed to manganese

The aim of this study was to assess the Mn toxicity to silver catfish considering Mn accumulation and oxidative status in different tissues, as well as pituitary hormone expression after acclimation to hypoxia. Silver catfish acclimated to hypoxia for 10 days and successively exposed to Mn (9.8mgL−1) for an additional 10 days exhibited lower Mn accumulation in plasma, liver, kidneys and brain and prevented the hematocrit decrease observed in the normoxia group. Hypoxia acclimation also modified Mn-induced oxidative damage, which was observed by lower reactive species (RS) generation in gills and kidneys, decreased lipid peroxidation (LP) levels in gills, liver and kidneys and decreased protein carbonyl (PC) levels in liver, kidneys and brain. Manganese accumulation showed positive correlations with LP levels in gills and kidneys, as well as with PC levels in gills, liver and brain. In addition, hypoxia acclimation and Mn exposure increased catalase (CAT) activity in gills and kidneys and Na+/K+-ATPase activity in gills, liver and brain. Silver catfish that were acclimated under normoxia and exposed to Mn displayed increased pituitary prolactin (PRL) and decreased somatolactin (SL) expression. Interestingly, hypoxia acclimation prevented hormonal fluctuation of PRL and SL in fish exposed to Mn. These findings indicate that while the exposure of silver catfish to Mn under normoxia was related to metal accumulation and oxidative damage in tissues together with endocrine axis disruption, as represented by PRL and SL, hypoxia acclimation reduced waterborne Mn uptake, thereby minimizing oxidative damage and changes in hormonal profile. We hypothesized that moderate hypoxia is able to generate adaptive responses, which may be related to hormesis, thereby ameliorating Mn toxicity to silver catfish.

Carbofuran induced oxidative stress mediated alterations in Na⁺-K⁺-ATPase activity in rat brain: amelioration by vitamin E.

Pesticides cause oxidative stress and adversely influence Na(+)-K(+)-ATPase activity in animals. Since impact of carbofuran has not been properly studied in the mammalian brain, the ability of carbofuran to induce oxidative stress and modulation in Na(+)-K(+)-ATPase activity and its amelioration by vitamin E was performed. The rats divided into six groups received two different doses of carbofuran (15% and 30% LD50) for 15 days. The results suggested that the carbofuran treatment caused a significant elevation in levels of malonaldehyde and reduced glutathione and sharp inhibition in the activities of super oxide dismutase, catalase, and glutathione-S-transferase; the effect being dose dependent. Carbofuran at different doses also caused sharp reduction in the activity of Na(+)-K(+)-ATPase. The pretreatment of vitamin E, however, showed a significant recovery in these indices. The pretreatment of rats with vitamin E offered protection from carbofuran-induced oxidative stress.

Delayed administration of zingerone mitigates the behavioral and histological alteration via repression of oxidative stress and intrinsic programmed cell death in focal transient ischemic rats

The neuronal mitochondria succumb to ischemia–reperfusion injury and release huge amount of reactive oxygen species and ultimately lead the neurons to intrinsic pathway of programmed cell death (iPCD). The present study was undertaken to elucidate the ischemia–reperfusion-induced oxidative stress and molecular events in iPCD 24h post ischemia–reperfusion injury and plausible mitigation by zingerone, a potent antioxidant of ginger rhizome. The right middle cerebral artery was occluded for 2h followed by reperfusion for 22hours. A maximum infarct volume (43.29%) and mitochondrial injury (56.99%) was observed in middle cerebral artery occlusion (MCAO) group. However, zingerone administration (50 and 100mg/kg b.wt. orally twice) at 5h and 12h from initiation of MCAO showed a significant reduction in infarct volume and mitochondrial injury (p<0.001). Zingerone treatment significantly improved behavioral outputs (p<0.05) and histological architecture (p<0.001) by reducing lipid peroxidation (p<0.01), augmenting the reduced glutathione content (p<0.01) and restoring Na+-K+ ATPase and superoxide dismutase activities (p<0.01) in MCAO brain. Zingerone successfully reduced the caspase-3 and -9 activities in MCAO group (p<0.05) and succeeded in lowering the expressions of pro-apoptotic proteins — Apaf-1 and Bax (p<0.001). The present study suggests that zingerone is a potent antioxidant that salvaged the ischemic penumbral zone neurons by inhibiting iPCD and oxidative stress.

Study of antidepressant-like activity of an enriched phloroglucinol fraction obtained from Hypericum caprifoliatum

Context: Hypericum caprifoliatum Cham & Schlecht (Guttiferae) extracts have a potential antidepressant-like effect in rodents. However, the molecular mechanisms by which these extracts exert this effect remain unclear.Objective: This study evaluated the effect of HC1, a fraction obtained from H. caprifoliatum enriched in phloroglucinol derivatives, on the Na+, K+ ATPase activity in mouse brain and verified the influence of veratrine on the effect of HC1 in the forced swimming test (FST).Materials and methods: Veratrine (0.06 mg/kg) and HC1 (360 mg/kg) were given alone or combined i.p. 60 and p.o. 30 min, respectively, before FST. The effect of single and repeated administration (once a day for 3 consecutive days) of HC1 (360 mg/kg) on Na+, K+ ATPase activity was evaluated ex vivo in the cerebral cortex and hippocampus of mice subjected or not to FST.Results: HC1 reduced the immobility time (103.15 ± 18.67 s), when compared to the control group (183.6 ± 9.51 s). This effect was prevented by veratrine (151.75 ± 22.19 s). Mice repeatedly treated with HC1 presented a significant increase in Na+, K+ ATPase activity, both in cerebral cortex (46 ± 2.41 nmol Pi/minċmg protein) and hippocampus (49.83 ± 2.31 nmol Pi/minċmg protein), in relation to the respective controls (30 ± 2.66 and 29.83 ± 2.31 nmol Pi/minċmg protein respectively).Discussion and conclusion: The HC1 antidepressant-like effect on FST might be related to its capacity to inhibit Na+ influx. HC1 increases hippocampal and cortical Na+, K+ ATPase activities possibly through long-term regulatory mechanisms.

Alteration of aluminium inhibition of synaptosomal (Na+/K+)ATPase by colestipol administration

The ability of aluminium to inhibit the (Na+/K+)ATPase activity has been observed by several authors. During chronic dietary exposure to AlCl3, brain (Na+/K+)ATPase activity drops, even if no alterations of catalytic subunit protein expression and of energy charge potential are observed. The aluminium effect on (Na+/K+)ATPase activity seems to implicate the reduction of interacting protomers within the oligomeric ensemble of the membrane-bound (Na+/K+)ATPase. The activity of (Na+/K+)ATPase is altered by the microviscosity of lipid environment. We studied if aluminium inhibitory effect on (Na+/K+)ATPase is modified by alterations in synaptosomal membrane cholesterol content. Adult male Wistar rats were submitted to chronic dietary AlCl3 exposure (0.03g/day of AlCl3) and/or to colestipol, a hypolidaemic drug (0.31g/day) during 4months. The activity of (Na+/K+)ATPase was studied in brain cortex synaptosomes with different cholesterol contents. Additionally, we incubate synaptosomes with methyl-β-cyclodextrin for both enrichment and depletion of membrane cholesterol content, with or without 300μM AlCl3. This enzyme activity was significantly reduced by micromolar AlCl3 added in vitro and when aluminium was orally administered to rats. The oral administration of colestipol reduced the cholesterol content and concomitantly inhibited the (Na+/K+)ATPase. The aluminium inhibitory effect on synaptosomal (Na+/K+)ATPase was reduced by cholesterol depletion both in vitro and in vivo.

Neuroprotective Effects of Ultra-Low-Molecular-Weight Heparin on Cerebral Ischemia/Reperfusion Injury in Rats: Involvement of Apoptosis, Inflammatory Reaction and Energy Metabolism

Previous experiments showed that ultra-low-molecular-weight heparin (ULMWH) reduced the infarct and neurologic deficit in rats followed by transient cerebral ischemia, but the mechanisms of its neuroprotective effect are unclear. This study reported the effect of ULMWH on energy metabolism, inflammatory reaction and neuronal apoptosis. Male Wistar rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 24 h. ULMWH (0.5, 1 mg/kg, i.v.) was administered after the MCAO and reperfusion. 24 h after the reperfusion, Spectrophotometric assay was used to determine the activity of ATPase and the content of lactic acid in the brain. The ICAM-1 and Caspase-3 genes were investigated by RT-PCR. Furthermore, the apoptotic percentage of cells in hippocampus was quantified by flow cytometry. Compared with the model group, ULMWH significantly decreased lactic acid content and increased ATPase activity in ischemic brain. At the same time, ULMWH inhibited the neural apoptosis and decreased the expressions of ICAM-1 and Caspase-3 mRNA in hippocampus. These findings suggest that ULMWH exhibits a neuroprotective effect against cerebral ischemia/reperfusion injury, partly through improving energy metabolism, inhibiting apoptosis and attenuating inflammatory reaction.

Sub-lethal effects of titanium dioxide nanoparticles on the physiology and reproduction of zebrafish

There are limited data on the sub-lethal physiological effects of titanium dioxide nanoparticles (TiO2 NPs) in adult fishes, and the consequences of TiO2 NP exposure on reproductive success are also unclear. This study aimed to examine the sub-lethal effects of a 14-d aqueous TiO2 (TiO2 NP, 0.1 or 1.0mgl−1; TiO2 bulk, 1.0mgl−1) exposure on the physiology and reproductive health of zebrafish. After the 14-d exposure, fish were examined for haematology, whole body electrolyte and trace metal profiles, biochemistry, and histopathology. Then, during a 21-d post exposure recovery period, effects of the TiO2 exposure on reproductive success were evaluated. Whole body Ti concentrations increased significantly in fish exposed to both the 1.0mgl−1 TiO2 NP and bulk TiO2 compared to controls, but concentrations returned to control levels by the end of the recovery period. No change in erythrocyte counts were observed, but there was a two-fold decline in leukocyte counts in all TiO2 treatment groups relative to time-matched controls. Whole body electrolyte and trace metal profiles were not affected by exposure to TiO2, and there were no changes in Na+K+-ATPase activity in brain, gill or liver tissues. Total glutathione (GSH) levels in brain, gill and liver tissues were higher in fish exposed to TiO2 NP (both 0.1 and 1.0mgl−1) compared to bulk TiO2 and control fish. Histological examination of gill, liver, brain and gonad tissues showed little evidence of treatment-related morphological change. At the end of the 14-d exposure adult zebrafish were able to reproduce; however, the cumulative number of viable embryos produced was lower in fish exposed to 1.0mgl−1 TiO2 (both NP and bulk) by the end of the 21-d recovery period. Overall, this study showed limited toxicity of bulk or nano scale TiO2 during the exposure; however reproduction was affected in both bulk and NP 1.0mgl−1 groups.

Short-term mercury exposure on Na+/K+-ATPase activity and ionoregulation in gill and brain of an Indian major carp, Cirrhinus mrigala

Recently mercury pollution has been increased considerably in aquatic resources throughout the world and it is a growing global concern. In this study, the 96h LC50 value of waterborne mercuric chloride for Cirrhinus mrigala was found to be 0.34mg/L (with 95% confidence limits). Fingerlings of C. mrigala were exposed to 0.068 and 0.034mg/L of mercuric chloride for 96h to assess the Na+/K+-ATPase activity and ionoregulation (Na+, K+ and Cl−) in gill and brain. Results showed that Na+/K+-ATPase activity and ionic levels (Na+, K+ and Cl−) in gill and brain of fish exposed to different concentrations of mercuric chloride were found to be significantly (p<0.05) decreased throughout the study period. Mercury inactivates many enzymes by attaching to sulfur atoms in which the enzyme Na+/K+-ATPase is highly sensitive to mercury. The inhibition of gill and brain Na+/K+-ATPase activity might have resulted from the physicochemical alteration of the membrane due to mercury toxicity. Moreover, inhibition of Na+/K+-ATPase may affect the ion transport and osmoregulatory function by blocking the transport of substances across the membrane by active transport. The present study indicates that the alterations in these parameters can be used in environmental biomonitoring of mercury contamination in aquatic ecosystem.

MK-801 alters Na+, K+-ATPase activity and oxidative status in zebrafish brain: reversal by antipsychotic drugs

Schizophrenia is a debilitating mental disorder with a global prevalence of 1% and its etiology remains poorly understood. In the current study we investigated the influence of antipsychotic drugs on the effects of MK-801 administration, which is a drug that mimics biochemical changes observed in schizophrenia, on Na(+), K(+)-ATPase activity and some parameters of oxidative stress in zebrafish brain. Our results showed that MK-801 treatment significantly decreased Na(+), K(+)-ATPase activity, and all antipsychotics tested prevented such effects. Acute MK-801 treatment did not alter reactive oxygen/nitrogen species by 2'7'-dichlorofluorscein (H2DCF) oxidation assay, but increased the levels of thiobarbituric acid reactive substances (TBARS), when compared with controls. Some antipsychotics such as sulpiride, olanzapine, and haloperidol prevented the increase of TBARS caused by MK-801. These findings indicate oxidative damage might be a mechanism involved in the decrease of Na(+), K(+)-ATPase activity induced by MK-801. The parameters evaluated in this study had not yet been tested in this animal model using the MK-801, suggesting that zebrafish is an animal model that can contribute for providing information on potential treatments and disease characteristics.

3-Methylcrotonylglycine disrupts mitochondrial energy homeostasis and inhibits synaptic Na(+),K (+)-ATPase activity in brain of young rats.

Deficiency of 3-methylcrotonyl-CoA carboxylase activity is an inherited metabolic disease biochemically characterized by accumulation and high urinary excretion of 3-methylcrotonylglycine (3MCG), and also of 3-hydroisovalerate in lesser amounts. Affected patients usually have neurologic dysfunction, brain abnormalities and cardiomyopathy, whose pathogenesis is still unknown. The present study investigated the in vitro effects of 3MCG on important parameters of energy metabolism, including CO(2) production from labeled acetate, enzyme activities of the citric acid cycle, as well as of the respiratory chain complexes I-IV (oxidative phosphorylation), creatine kinase (intracellular ATP transfer), and synaptic Na(+),K(+)-ATPase (neurotransmission) in brain cortex of young rats. 3MCG significantly reduced CO(2) production, implying that this compound compromises citric acid cycle activity. Furthermore, 3MCG diminished the activities of complex II-III of the respiratory chain, mitochondrial creatine kinase and synaptic membrane Na(+),K(+)-ATPase. Furthermore, antioxidants were able to attenuate or fully prevent the inhibitory effect of 3MCG on creatine kinase and synaptic membrane Na(+),K(+)-ATPase activities. We also observed that lipid peroxidation was elicited by 3MCG, suggesting the involvement of free radicals on 3MCG-induced effects. Considering the importance of the citric acid cycle and the electron flow through the respiratory chain for brain energy production, creatine kinase for intracellular energy transfer, and Na(+),K(+)-ATPase for the maintenance of the cell membrane potential, the present data indicate that 3MCG potentially impairs mitochondrial brain energy homeostasis and neurotransmission. It is presumed that these pathomechanisms may be involved in the neurological damage found in patients affected by 3-methylcrotonyl-CoA carboxylase deficiency.

Anti-hypoxic activity at simulated high altitude was isolated in petroleum ether extract of Saussurea involucrata

Ethnopharmacological relevanceRhodiola algida, Saussurea involucrata, and other herbs grown in Qinghai-Tibetan plateau have long been used to prevent and treat acute mountain sickness. Aim of the studyTo screen and identify the anti-hypoxic constituents in the herbs grown in Qinghai-Tibetan plateau of Northwestern China. Materials and methodsThe anti-hypoxic activities of 20 selected plateau herbs were examined against two positive controls, Rhodiola algida and acetazolamide, using the normobaric hypoxia model of mice. The herb with the highest activity was successively extracted with 70% ethanol, petroleum ether, chloroform, ethyl acetate and n-butanol. The extract with the highest activity was identified by comparing the survival time of mice under normobaric hypoxia condition after being subjected to different extracts. The identified extract was further tested by simulating high altitudes through an acute decompression model and a chronic decompression model for mice. ResultsThe herb found to have the highest anti-hypoxic activity was Saussurea involucrate (Kar. et Kir.) Sch.-Bip, and the most effective fraction was in the petroleum ether extract. Administration of petroleum ether extract of Saussurea involucrata (PESI) to mice at 50mg/kg significantly decreased the mortality of animals under acute decompression conditions. Changes in biochemical indicators for glycometabolism and energy metabolism, including adenosine triphosphate (ATP) content and adenosine triphosphatase (ATPase) activity in brain and cardiac muscle, lactic acid (LAC) and lactate dehydrogenase (LDH) in blood and cardiac muscles, blood sugar, and glycogen content in liver and skeletal muscle were reversed under chronic decompression conditions. ConclusionsSaussurea involucrata (Kar. et Kir.) Sch.-Bip exhibits high anti-hypoxic activity that may be effective in preventing acute mountain sickness, and the active constituents are mainly in the petroleum ether extract.