scholarly journals Effect of Intrahippocampal Administration of α7 Subtype Nicotinic Receptor Agonist PNU-282987 and Its Solvent Dimethyl Sulfoxide on the Efficiency of Hypoxic Preconditioning in Rats

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7387
Author(s):  
Elena I. Zakharova ◽  
Andrey T. Proshin ◽  
Mikhail Y. Monakov ◽  
Alexander M. Dudchenko
Keyword(s):  
Dimethyl Sulfoxide ◽  
Pharmacological Study ◽  
Acoustic Startle ◽  
Intraperitoneal Administration ◽  
Hypoxic Preconditioning ◽  
Moderate Hypobaric Hypoxia ◽  
Cholinergic Signaling ◽  
Ca1 Area

We have previously suggested a key role of the hippocampus in the preconditioning action of moderate hypobaric hypoxia (HBH). The preconditioning efficiency of HBH is associated with acoustic startle prepulse inhibition (PPI). In rats with PPI > 40%, HBH activates the cholinergic projections of hippocampus, and PNU-282987, a selective agonist of α7 nicotinic receptors (α7nAChRs), reduces the HBH efficiency and potentiating effect on HBH of its solvent dimethyl sulfoxide (DMSO, anticholinesterase agent) when administered intraperitoneally. In order to validate the hippocampus as a key structure in the mechanism of hypoxic preconditioning and research a significance of α7nAChR activation in the hypoxic preconditioning, we performed an in vivo pharmacological study of intrahippocampal injections of PNU-282987 into the CA1 area on HBH efficiency in rats with PPI ≥ 40%. We found that PNU-282987 (30 μM) reduced HBH efficiency as with intraperitoneal administration, while DMSO (0.05%) still potentiated this effect. Thus, direct evidence of the key role of the hippocampus in the preconditioning effect of HBH and some details of this mechanism were obtained in rats with PPI ≥ 40%. The activation of α7nAChRs is not involved in the cholinergic signaling initiated by HBH or DMSO via any route of administration. Possible ways of the potentiating action of DMSO on HBH efficiency and its dependence on α7nAChRs are discussed.

THE ROLE OF RIBOFLAVIN IN MONOAMINE OXIDASE ACTIVITY

1963 ◽  
Vol 41 (1) ◽  
pp. 57-64 ◽  
Author(s):  
M. H. Wiseman-Distler ◽  
T. L. Sourkes
Keyword(s):  
Monoamine Oxidase ◽  
De Novo ◽  
Intraperitoneal Administration ◽  
Enzymatic System ◽  
Irreversible Inhibitor ◽  
Riboflavin Deficiency ◽  
Deficient Diet ◽  
Hydroxyindoleacetic Acid

The role of riboflavin in the activity of monoamine oxidase (MAO) was investigated by omitting the vitamin from the diet of rats which were further treated with iproniazid, an irreversible inhibitor of the enzyme. The rate of recovery from the inhibition, presumably reflecting de novo synthesis of the enzyme, was estimated by measuring the excretion of the acidic metabolites formed after intraperitoneal administration of serotonin (5 HT) and dopamine. Consumption of the deficient diet did not impair the action of MAO on these amines. After injection of iproniazid, return to control levels of MAO activity was slower when measured by the oxidation of dopamine than of 5 HT; there was a small but significant effect of riboflavin deficiency upon the conversion of 5 HT to 5-hydroxyindoleacetic acid. This was probably due to enhanced inhibition of MAO observed in deficient rats, an effect that was also obtained when inhibitors other than iproniazid were used in vivo. Similarly, disappearance of 5 HT during incubation with a supernatant prepared from liver of deficient rats was also affected to a greater extent by these inhibitors than when the enzymatic system was prepared from control livers. This finding suggests that riboflavin deficiency renders MAO more susceptible to inhibition.

Perspective of strategic plasma therapy for prognostic improvement of patients with ovarian cancer

2013 ◽  
Vol 1598 ◽  
Author(s):  
Hiroaki Kajiyama ◽  
Fumi Utsumi ◽  
Kae Nakamura ◽  
Hiromasa Tanaka ◽  
Masaru Hori ◽  
...  
Keyword(s):  
Atmospheric Pressure ◽  
Antitumor Effect ◽  
Intraperitoneal Administration ◽  
Atmospheric Pressure Plasma ◽  
Plasma Therapy ◽  
Intracellular Mechanism ◽  
Patients Experience

ABSTRACTEpithelial ovarian carcinoma (EOC) is the leading cause of cancer-related death in women in Western countries. Once patients experience recurrence, complete cure is almost impossible. We elucidated the effect of nonequilibrium atmospheric pressure plasma on the growth of EOC, particularly in plasma-activated medium (PAM). Furthermore, we examined the role of reactive oxygen species (ROS) or their scavengers in chronic antineoplastic-resistant EOC cells. As a result, we showed PAM induced the antitumor effect of EOC cells in vitro and in vivo, even in chemoresistant cells. To apply the plasma treatment for advanced or recurrent EOC, we suggest adopting indirect plasma therapy instead of direct plasma considering intraperitoneal administration in the future. However, there are several problems under investigation, including intracellular mechanism of antitumor effect by PAM and adverse event in vivo.

Nitrite Oxidase Activities of Cytochrome P450 and Mitochondria

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5310-5310
Author(s):  
Erin Curtis ◽  
Lewis L Hsu ◽  
Yuen Yi Hon ◽  
Lisa Geary ◽  
Audrey C Noguchi ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Intraperitoneal Administration ◽  
Biological Responses ◽  
Iron Nitrosyl ◽  
Organ Systems ◽  
Major Organ ◽  
Nitrite Uptake ◽  
Rats And Mice

Abstract Abstract 5310 Once dismissed as an inert byproduct of nitric oxide (NO) auto-oxidation, nitrite (NO2−) is now accepted as an endocrine reserve of NO that elicits a number of fundamental biological responses in all major organ systems. While it is known that tissue nitrite is derived from both oxidation of NO and from dietary nitrite and nitrate, much less is known about how nitrite is metabolized by tissue or about the factors that influence this metabolism. Here we investigate the rates and mechanisms by which nitrite is metabolized by tissue over a range of oxygen tensions in rats and mice. We show that the rate of nitrite metabolism differs in heart, liver, lung and brain tissue. Further, oxygen regulates the rate and products of nitrite metabolism in each of these tissues. In hypoxic tissue, nitrite is predominantly reduced to NO, with significant formation of iron-nitrosyl heme proteins and S-nitrosothiols. Interestingly, this hypoxic nitrite metabolism is mediated by different sets of nitrite reductase enzymes in each tissue. In contrast, tissue consumption of nitrite is more rapid in normoxia and the major end product is nitrate. While cytochrome P450s and myoglobin contributed in the liver and heart respectively, mitochondrial cytochrome c oxidase played a significant role in this normoxic nitrite oxidation, which could be completely inhibited by cyanide in all tissues. We used cyanide-based nitrite preservation solution to measure the pharmacokinetics of oral and intraperitoneally administered nitrite in vivo. Using this methodology, we measured basal levels of nitrite in the major tissues and confirm that the heart contains the greatest concentration of nitrite, followed by the liver and finally the lung. We demonstrate that intraperitoneal administration of nitrite to mice increases nitrite levels most significantly in the liver and heart, where nitrite uptake is rapid (5–10 min) and steadily decreases thereafter, such that levels are back to baseline by 30 min. Little to no increase was observed in the lung. In these studies, changes in nitrate were difficult to detect due to the high levels of basal nitrate present in vivo and low concentration of nitrite administered. However, the rapid metabolism of nitrite in the tissue suggests that oxidation is at least partially responsible. In contrast to intraperitoneal nitrite, oral nitrite increased nitrite levels in all organs of mice, an effect which peaked in all organs except liver at 3 days. Collectively, these data provide insight into the fate of nitrite in tissue, the enzymes involved in hypoxic and normoxic nitrite metabolism and the role of oxygen in regulating these processes. Disclosures: No relevant conflicts of interest to declare.

Regulation of prostaglandin biosynthesis in vivo by glutathione

1998 ◽  
Vol 274 (2) ◽  
pp. R294-R302 ◽  
Author(s):  
Alon Margalit ◽  
Scott D. Hauser ◽  
Ben S. Zweifel ◽  
Melissa A. Anderson ◽  
Peter C. Isakson
Keyword(s):  
Reduced Glutathione ◽  
Intraperitoneal Administration ◽  
Peritoneal Macrophages ◽  
Urate Crystal ◽  
Cox 2 ◽  
Cox 1 ◽  
Urate Crystals

Intraperitoneal administration of urate crystals to mice reduced subsequent macrophage conversion of arachidonic acid (AA) to prostaglandins (PGs) and 12-hydroxyeicosatetraenoic acid for up to 6 h. In contrast, levels of 12-hydroxyheptadecatrienoic acid (12-HHT) were markedly elevated. This metabolic profile was previously observed in vitro when recombinant cyclooxygenase (COX) enzymes were incubated with reduced glutathione (GSH). Analysis of peritoneal GSH levels revealed a fivefold elevation after urate crystal administration. The GSH synthesis inhibitorl-buthionine-[ S, R]-sulfoximine partially reversed the urate crystal effect on both GSH elevation and PG synthesis. Moreover, addition of exogenous GSH to isolated peritoneal macrophages shifted AA metabolism from PGs to 12-HHT. Urate crystal administration reduced COX-1, but induced COX-2 expression in peritoneal cells. The reduction of COX-1 may contribute to the attenuation of PG synthesis after 1 and 2 h, but PG synthesis remained inhibited up to 6 h, when COX-2 levels were high. Overall, our results indicate that elevated GSH levels inhibit PG production in this model and provide in vivo evidence for the role of GSH in the regulation of PG biosynthesis.

Dimethyl sulfoxide decreases interleukin-8-mediated neutrophil recruitment in the airways

1996 ◽  
Vol 271 (5) ◽  
pp. L838-L843 ◽  
Author(s):  
P. P. Massion ◽  
A. Linden ◽  
H. Inoue ◽  
M. Mathy ◽  
K. M. Grattan ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Epithelial Cells ◽  
Dimethyl Sulfoxide ◽  
Neutrophil Recruitment ◽  
Interleukin 8 ◽  
Bronchial Epithelial ◽  
Anti Inflammatory

In this study, we investigated the role of dimethyl sulfoxide (DMSO) in inhibiting interleukin-8 (IL-8)-mediated neutrophil recruitment induced by Pseudomonas aeruginosa (PA) bacterial supernatant. First, we tested whether DMSO could inhibit IL-8 production induced by PA in human bronchial epithelial (16-HBE) cells in vitro. In these cells, exposure to PA or H2O2 induced IL-8 production dose dependently, an effect that was inhibited by 1% DMSO at both the protein and RNA level. Second, we tested whether DMSO could block the recruitment of neutrophils induced by PA in a bypassed segment of dog trachea in vivo. PA supernatant was placed in the tracheal segment for 6 h in four dogs, and neutrophil recruitment and IL-8 concentrations were measured in the superfusate. DMSO prevented the recruitment of neutrophils and IL-8 production induced by PA time dependently. The results suggest that DMSO may play an anti-inflammatory role in the airway by inhibiting IL-8 production in epithelial cells.

scholarly journals The protective role of endogenously synthesized nitric oxide in staphylococcal enterotoxin B-induced shock in mice.

1994 ◽  
Vol 180 (3) ◽  
pp. 1153-1158 ◽  
Author(s):  
S Florquin ◽  
Z Amraoui ◽  
C Dubois ◽  
J Decuyper ◽  
M Goldman
Keyword(s):  
Nitric Oxide ◽  
Intraperitoneal Administration ◽  
Serum Levels ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Protective Effects ◽  
Ifn Gamma ◽  
Enterotoxin B

Nitric oxide (NO) synthesis during experimental endotoxemia has been shown to have both deleterious and beneficial effects. In the present study, we analyzed the in vivo production and the regulatory role of NO in the shock syndrome induced by staphylococcal enterotoxin B (SEB) in mice. First, we found that intraperitoneal administration of 100 micrograms SEB in BALB/c mice induced a massive synthesis of NO as indicated by high serum levels of nitrite (NO2-) and nitrate (NO3-) peaking 16 h after SEB injection. The inhibition of NO2- and NO3- release in mice injected with anti-tumor necrosis factor (TNF) and/or anti-interferon gamma (IFN-gamma) monoclonal antibody (mAb) before SEB challenge revealed that both cytokines were involved in SEB-induced NO overproduction. In vitro experiments indicated that NO synthase (NOS) inhibition by N-nitro-L-arginine methyl ester (L-NAME) enhanced IFN-gamma and TNF production by splenocytes in response to SEB. A similar effect was observed in vivo as treatment of mice with L-NAME resulted in increased IFN-gamma and TNF serum levels 24 h after SEB challenge, together with persistent expression of corresponding cytokine mRNA in spleen. The prolonged production of inflammatory cytokines in mice receiving L-NAME and SEB was associated with a 95% mortality rate within 96 h, whereas all mice survived injections of SEB or L-NAME alone. Both TNF and INF-gamma were responsible for the lethality induced by SEB in L-NAME-treated mice as shown by the protection provided by simultaneous administration of anti-IFN-gamma and anti-TNF mAbs. We conclude the SEB induces NO synthesis in vivo and that endogenous NO has protective effects in this model of T cell-dependent shock by downregulating IFN-gamma and TNF production.

scholarly journals The formin Fmn2 is required for the development of an excitatory interneuron module in the zebrafish acoustic startle circuit

2020 ◽  
Author(s):  
Dhriti Nagar ◽  
Tomin K James ◽  
Ratnakar Mishra ◽  
Shrobona Guha ◽  
Aurnab Ghose
Keyword(s):  
Growth Cone ◽  
Neurodevelopmental Disorders ◽  
High Speed ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Video Recording ◽  
Acoustic Startle ◽  
Neuronal Cultures

ABSTRACTThe formin family member, Fmn2, is a neuronally enriched cytoskeletal remodelling protein conserved across vertebrates. Recent studies have implicated Fmn2 in neurodevelopmental disorders, including sensory processing dysfunction and intellectual disability in humans. Cellular characterization of Fmn2 in primary neuronal cultures has identified its function in the regulation of cell-substrate adhesion and consequently growth cone translocation. However, the role of Fmn2 in the development of neural circuits in vivo, and its impact on associated behaviours have not been tested.Using automated analysis of behaviour and systematic investigation of the associated circuitry, we uncover the role of Fmn2 in zebrafish neural circuit development. As reported in other vertebrates, the zebrafish ortholog of Fmn2 is also enriched in the developing zebrafish nervous system. We find that Fmn2 is required for the development of an excitatory interneuron pathway, the spiral fiber neuron, which is an essential circuit component in the regulation of the Mauthner cell-mediated acoustic startle response. Consistent with the loss of the spiral fiber neurons tracts, high-speed video recording revealed a reduction in the short latency escape events while responsiveness to the stimuli was unaffected.Taken together, this study provides evidence for a circuit-specific requirement of Fmn2 in eliciting an essential behaviour in zebrafish. Our findings underscore the importance of Fmn2 in neural development across vertebrate lineages and highlight zebrafish models in understanding neurodevelopmental disorders.SIGNIFICANCE STATEMENTFmn2 is a neuronally enriched cytoskeletal remodelling protein linked to neurodevelopment and cognitive disorders in humans. Recent reports have characterized its function in growth cone motility and chemotaxis in cultured primary neurons. However, the role of Fmn2 in the development of neural circuits in vivo and its implications in associated behaviours remain unexplored. This study shows that Fmn2 is required for the development of neuronal processes in the acoustic startle circuit to ensure robust escape responses to aversive stimuli in zebrafish. Our study underscores the crucial role of the non-diaphanous formin, Fmn2, in establishing neuronal connectivity and related behaviour in zebrafish.

scholarly journals The Role of Dimethyl Sulfoxide (DMSO) in Gene Expression Modulation and Glycosaminoglycan Metabolism in Lysosomal Storage Disorders on an Example of Mucopolysaccharidosis

2019 ◽  
Vol 20 (2) ◽  
pp. 304 ◽  
Author(s):  
Marta Moskot ◽  
Joanna Jakóbkiewicz-Banecka ◽  
Anna Kloska ◽  
Ewa Piotrowska ◽  
Magdalena Narajczyk ◽  
...  
Keyword(s):  
Dimethyl Sulfoxide ◽  
Human Fibroblasts ◽  
Transcriptional Level ◽  
Lysosomal Storage ◽  
Biological Studies ◽  
Dmso Treatment ◽  
Cellular Pathways ◽  
Glycosaminoglycan Metabolism

Obstacles to effective therapies for mucopolysaccharidoses (MPSs) determine the need for continuous studies in order to enhance therapeutic strategies. Dimethyl sulfoxide (DMSO) is frequently utilised as a solvent in biological studies, and as a vehicle for drug therapy and the in vivo administration of water-insoluble substances. In the light of the uncertainty on the mechanisms of DMSO impact on metabolism of glycosaminoglycans (GAGs) pathologically accumulated in MPSs, in this work, we made an attempt to investigate and resolve the question of the nature of GAG level modulation by DMSO, the isoflavone genistein solvent employed previously by our group in MPS treatment. In this work, we first found the cytotoxic effect of DMSO on human fibroblasts at concentrations above 3%. Also, our results displayed the potential role of DMSO in the regulation of biological processes at the transcriptional level, then demonstrated a moderate impact of the solvent on GAG synthesis. Interestingly, alterations of lysosomal ultrastructure upon DMSO treatment were visible. As there is growing evidence in the literature that DMSO can affect cellular pathways leading to numerous changes, it is important to expand our knowledge concerning this issue.

THE ROLE OF RIBOFLAVIN IN MONOAMINE OXIDASE ACTIVITY

1963 ◽  
Vol 41 (1) ◽  
pp. 57-64 ◽  
Author(s):  
M. H. Wiseman-Distler ◽  
T. L. Sourkes
Keyword(s):  
Monoamine Oxidase ◽  
De Novo ◽  
Intraperitoneal Administration ◽  
Enzymatic System ◽  
Irreversible Inhibitor ◽  
Riboflavin Deficiency ◽  
Deficient Diet ◽  
Hydroxyindoleacetic Acid

The role of riboflavin in the activity of monoamine oxidase (MAO) was investigated by omitting the vitamin from the diet of rats which were further treated with iproniazid, an irreversible inhibitor of the enzyme. The rate of recovery from the inhibition, presumably reflecting de novo synthesis of the enzyme, was estimated by measuring the excretion of the acidic metabolites formed after intraperitoneal administration of serotonin (5 HT) and dopamine. Consumption of the deficient diet did not impair the action of MAO on these amines. After injection of iproniazid, return to control levels of MAO activity was slower when measured by the oxidation of dopamine than of 5 HT; there was a small but significant effect of riboflavin deficiency upon the conversion of 5 HT to 5-hydroxyindoleacetic acid. This was probably due to enhanced inhibition of MAO observed in deficient rats, an effect that was also obtained when inhibitors other than iproniazid were used in vivo. Similarly, disappearance of 5 HT during incubation with a supernatant prepared from liver of deficient rats was also affected to a greater extent by these inhibitors than when the enzymatic system was prepared from control livers. This finding suggests that riboflavin deficiency renders MAO more susceptible to inhibition.

scholarly journals Opposite Pathways of Cholinergic Mechanisms of Hypoxic Preconditioning in the Hippocampus: Participation of Nicotinic α7 Receptors and Their Association with the Baseline Level of Startle Prepulse Inhibition

2020 ◽  
Vol 11 (1) ◽  
pp. 12
Author(s):  
Elena I. Zakharova ◽  
Zinaida I. Storozheva ◽  
Andrey T. Proshin ◽  
Mikhail Yu. Monakov ◽  
Alexander M. Dudchenko
Keyword(s):  
Prepulse Inhibition ◽  
Pharmacological Study ◽  
Acoustic Startle ◽  
Brain Regions ◽  
Hypoxic Preconditioning ◽  
Water Soluble ◽  
Synaptic Membrane ◽  
Cholinergic Mechanisms ◽  
Chat Activity ◽  
Membrane Bound

(1) Background. A one-time moderate hypobaric hypoxia (HBH) has a preconditioning effect whose neuronal mechanisms are not studied well. Previously, we found a stable correlation between the HBH efficiency and acoustic startle prepulse inhibition (PPI). This makes it possible to predict the individual efficiency of HBH in animals and to study its potential adaptive mechanisms. We revealed a bi-directional action of nicotinic α7 receptor agonist PNU-282987 and its solvent dimethyl sulfoxide on HBH efficiency with the level of PPI > or < 40%. (2) The aim of the present study was to estimate cholinergic mechanisms of HBH effects in different brain regions. (3) Methods: in rats pretested for PPI, we evaluated the activity of synaptic membrane-bound and water-soluble choline acetyltransferase (ChAT) in the sub-fractions of ‘light’ and ‘heavy’ synaptosomes of the neocortex, hippocampus and caudal brainstem in the intact brain and after HBH. We tested the dose-dependent influence of PNU-282987 on the HBH efficiency. (4) Results: PPI level and ChAT activity correlated negatively in all brain structures of the intact animals, so that the values of the latter were higher in rats with PPI < 40% compared to those with PPI > 40%. After HBH, this ChAT activity difference was leveled in the neocortex and caudal brainstem, while for membrane-bound ChAT in the ‘light’ synaptosomal fraction of hippocampus, it was reversed to the opposite. In addition, a pharmacological study revealed that PNU-282987 in all used doses and its solvent displayed corresponding opposite effects on HBH efficiency in rats with different levels of PPI. (5) Conclusion: We substantiate that in rats with low and high PPI two opposite hippocampal cholinergic mechanisms are involved in hypoxic preconditioning, and both are implemented by forebrain projections via nicotinic α7 receptors. Possible causes of association between general protective adaptation, HBH, PPI, forebrain cholinergic system and hippocampus are discussed.

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