Hyperoxia increases H2O2 production by brain in vivo

1987 ◽  
Vol 63 (1) ◽  
pp. 353-358 ◽  
Author(s):  
T. Yusa ◽  
J. S. Beckman ◽  
J. D. Crapo ◽  
B. A. Freeman
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Catalase Activity ◽  
Intermediate Compound ◽  
H2o2 Production ◽  
H2o2 Concentration ◽  
Compound I ◽  
Central Nervous System Toxicity ◽  
Competitive Substrate

Hyperoxia and hyperbaric hyperoxia increased the rate of cerebral hydrogen peroxide (H2O2) production in unanesthetized rats in vivo, as measured by the H2O2-mediated inactivation of endogenous catalase activity following injection of 3-amino-1,2,4-triazole. Brain catalase activity in rats breathing air (0.2 ATA O2) decreased to 75, 61, and 40% of controls due to endogenous H2O2 production at 30, 60, and 120 min, respectively, after intraperitoneal injection of 3-amino-1,2,4-triazole. The rate of catalase inactivation increased linearly in rats exposed to 0.6 ATA O2 (3 ATA air), 1.0 ATA O2 (normobaric 100% O2) and 3.0 ATA O2 (3 ATA 100% O2) compared with 0.2 ATA O2 (room air). Catalase inactivation was prevented by pretreatment of rats with ethanol (4 g/kg), a competitive substrate for the reactive catalase-H2O2 intermediate, compound I. This confirmed that catalase inactivation by 3-amino-1,2,4-triazole was due to formation of the catalase-H2O2 intermediate, compound I. The linear rate of catalase inactivation allows estimates of the average steady-state H2O2 concentration within brain peroxisomes to be calculated from the formula: [H2O2] = 6.6 pM + 5.6 ATA-1 X pM X [O2], where [O2] is the concentration of oxygen in ATA that the rats are breathing. Thus the H2O2 concentration in brains of rats exposed to room air is calculated to be about 7.7 pM, rises 60% when O2 tension is increased to 100% O2, and increases 300% at 3 ATA 100% O2, where symptoms of central nervous system toxicity first become apparent. These studies support the concept that H2O2 is an important mediator of O2-induced injury to the central nervous system.

Regional H2O2 concentration in rat brain after hyperoxic convulsions

1990 ◽  
Vol 69 (5) ◽  
pp. 1761-1766 ◽  
Author(s):  
C. A. Piantadosi ◽  
L. G. Tatro
Keyword(s):  
Rat Brain ◽  
Catalase Activity ◽  
Ex Vivo ◽  
Brain Structures ◽  
H2o2 Production ◽  
H2o2 Concentration ◽  
Compound I ◽  
Irreversible Inhibitor ◽  
Before And After ◽  
The Central Nervous System

O2 toxicity of the central nervous system (CNS) may be a result of enhanced generation of reactive O2 species such as superoxide and H2O2 at high PO2. In this study, we measured H2O2 production in six regions of the rat brain before and after convulsions induced by hyperbaric hyperoxia (HBO). H2O2 concentration was determined ex vivo using a method based on the H2O2-dependent decline in catalase activity in the presence of the irreversible inhibitor of compound I, 3-amino-1,2,4-triazole. Regional catalase activity in the brain ranged from 0.029 +/- 0.004 to 0.055 +/- 0.004 mumol O2.min-1.micrograms DNA-1 in cerebellum and medulla-pons, respectively. In the presence of aminotriazole, catalase activity declined after HBO-induced convulsions to 26-45% of normoxic values. The rates of inactivation of catalase were used to predict average steady-state values for H2O2 concentration in different brain structures. Estimated H2O2 concentrations during HBO varied from 31 to 51 pM in cerebellum and posterior subcortex and represented increases of 2.2-7.3 times normoxic values. These findings suggest that H2O2 is an important mediator of selective neuronal vulnerability to CNS O2 toxicity.

Comparison on Reactivity of Fe(III) and AI(III) Compounds in the Presence of Hydrogen Peroxide: Its Relevance to Possible Origin for Central Nervous System Toxicity by Aluminum Ion

1995 ◽  
Vol 50 (7-8) ◽  
pp. 571-577 ◽  
Author(s):  
Yuzo Nishida ◽  
Sayo Ito
Keyword(s):  
Hydrogen Peroxide ◽  
Central Nervous System ◽  
Nervous System ◽  
High Activity ◽  
Furan Ring ◽  
Nitrilotriacetic Acid ◽  
Central Nervous System Toxicity ◽  
The Brain ◽  
System Toxicity

Abstract The iron(III) compounds with several aminocarboxylate chelates containing an aryl or furan substituent exhibit high activity in enhancement of the reactivity of hydrogen peroxide, leading to facile hydroxylation at benzene ring, and to degradation of furan ring, but no such activity was observed for the corresponding Al(III) compounds. These results were inter­preted in terms of the molecular orbital consideration, and lack of the activity of the Al(III) complexes was attributed to lack of electrophilic nature of the peroxide adduct due to the absence of a d-orbital: this may explain the fact that there were no tumors in Al-NTA (nitrilotriacetic acid)-treated rats. Based on the facts observed in this study, the decreased function of iron(III) ions for synthesizing neurotransmitters in the brain was assumed to be one of the possible origin for the neurotoxicity by injection of the Al(III) salts in vivo.

Enhanced in vivo H2O2 generation by rat kidney in glycerol-induced renal failure

1989 ◽  
Vol 257 (3) ◽  
pp. F440-F445 ◽  
Author(s):  
B. Guidet ◽  
S. V. Shah
Keyword(s):  
Hydrogen Peroxide ◽  
Renal Failure ◽  
Acute Renal Failure ◽  
Catalase Activity ◽  
Tissue Injury ◽  
Rat Kidney ◽  
Intermediate Compound ◽  
Treated Group ◽  
Compound I

Aminotriazole-mediated inhibition of catalase has been used in previous studies as a measure of in vivo changes in the hydrogen peroxide generation. Using this method, we found a significantly higher inhibition of renal catalase activity at various time points (30, 60, and 90 min) in glycerol-treated rats (a well-established model for myoglobinuric acute renal failure) compared with rats treated with aminotriazole alone. The greater inhibition in the glycerol-treated group was not due to differences in aminotriazole levels. We confirmed that catalase inactivation by aminotriazole was due to formation of catalase-hydrogen peroxide intermediate (compound I) because catalase inactivation was prevented by ethanol, a competitive substrate for compound I. There were no significant differences in the aminotriazole-induced inhibition of renal cortical catalase activity in control and uranyl nitrate-treated rats, suggesting that there was no enhanced generation of hydrogen peroxide in this model of acute renal failure. Taken together, these data provide evidence for enhanced generation of hydrogen peroxide in glycerol-induced acute renal failure and suggest that the enhanced generation of hydrogen peroxide in the glycerol-induced acute renal failure is not a result of nonspecific response to tissue injury.

Neuropharmacological Profile and Chemical Analysis of Moroccan Ormenis mixta L.

2018 ◽  
Vol 16 (S1) ◽  
pp. S55-S64
Author(s):  
G. Hajjaj ◽  
A. Bahlouli ◽  
M. Tajani ◽  
K. Alaoui ◽  
Y. Cherrah ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Body Weight ◽  
Traditional Medicine ◽  
Behavioral Tests ◽  
Phytochemical Screening ◽  
Activity Profile ◽  
Acute Toxicity Study ◽  
Pharmacological Studies

Ormenis mixta L. is traditionally used for central nervous system (CNS)-related diseases. Its anti-stress properties have received attention in Moroccan traditional medicine and aromatherapy. However, no pharmacological studies have yet been undertaken on this plant in Morocco. The present study provides a preliminary phytochemical screening and psychopharmacological profile of the essential oil and aqueous extract from Ormenis mixta L. by using behavioral tests in vivo, at graded doses. The result of this research shows that Ormenis mixta L. was safe up to 2 g/kg b.w. (body weight) in the acute toxicity study, possesses potential psychostimulant effect, and has antianxiety and antidepressant-like activity. This activity profile of Ormenis mixta L. was similar to the typical psychostimulant, caffeine. The exact mechanism of action underlying this stimulant-like effect should be clarified with further detailed studies. These results explained the extensive use of Ormenis mixta L. as a traditional medicine in Morocco.

scholarly journals Pharmacogenetics of the Central Nervous System—Toxicity and Relapse Affecting the CNS in Pediatric Acute Lymphoblastic Leukemia

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2333
Author(s):  
Judit C. Sági ◽  
András Gézsi ◽  
Bálint Egyed ◽  
Zsuzsanna Jakab ◽  
Noémi Benedek ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Gene Polymorphisms ◽  
Lymphoblastic Leukemia ◽  
Toxic Encephalopathy ◽  
Inverse Association ◽  
Central Nervous System Toxicity ◽  
Cns Relapse ◽  
The Central Nervous System

Despite improving cure rates in childhood acute lymphoblastic leukemia (ALL), therapeutic side effects and relapse are ongoing challenges. These can also affect the central nervous system (CNS). Our aim was to identify germline gene polymorphisms that influence the risk of CNS events. Sixty single nucleotide polymorphisms (SNPs) in 20 genes were genotyped in a Hungarian non-matched ALL cohort of 36 cases with chemotherapy related acute toxic encephalopathy (ATE) and 544 controls. Five significant SNPs were further analyzed in an extended Austrian-Czech-NOPHO cohort (n = 107 cases, n = 211 controls) but none of the associations could be validated. Overall populations including all nations’ matched cohorts for ATE (n = 426) with seizure subgroup (n = 133) and posterior reversible encephalopathy syndrome (PRES, n = 251) were analyzed, as well. We found that patients with ABCB1 rs1045642, rs1128503 or rs2032582 TT genotypes were more prone to have seizures but those with rs1045642 TT developed PRES less frequently. The same SNPs were also examined in relation to ALL relapse on a case-control matched cohort of 320 patients from all groups. Those with rs1128503 CC or rs2032582 GG genotypes showed higher incidence of CNS relapse. Our results suggest that blood-brain-barrier drug transporter gene-polymorphisms might have an inverse association with seizures and CNS relapse.

Monitoring of tricyclic antidepressant plasma levels and clinical response: a review of the literature. Part II

1989 ◽  
Vol 4 (2) ◽  
pp. 81-90 ◽  
Author(s):  
I.R. De Oliveira ◽  
P.A.S. Do Prado-Lima ◽  
B. Samuel-Lajeunesse
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Elderly Patients ◽  
Plasma Levels ◽  
Tricyclic Antidepressant ◽  
Review Of The Literature ◽  
Central Nervous System Toxicity ◽  
Routine Measurement ◽  
System Toxicity

SummaryPart II of this paper contains some general considerations on tricyclic antidepressant (TCA) monitoring. Long-term assessment of TCA plasma levels is advised by the few existent studies, although each of these focusses on different aspects. Cardiovascular and central nervous system toxicity is reviewed as well as pharmacokinetics and the importance of protein binding. Some consideration is also given to their use in elderly patients. The authors conclude that although available data support its usefulness in many situations, routine measurement of TCA levels is not warranted.

scholarly journals Plant Species of Sub-Family Valerianaceae—A Review on Its Effect on the Central Nervous System

Plants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 846
Author(s):  
Gitishree Das ◽  
Han-Seung Shin ◽  
Rosa Tundis ◽  
Sandra Gonçalves ◽  
Ourlad Alzeus G. Tantengco ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Plant Species ◽  
Current Knowledge ◽  
Biological Properties ◽  
In Vivo Studies ◽  
Food Species ◽  
The Central Nervous System ◽  
Preclinical And Clinical Studies

Valerianaceae, the sub-family of Caprifoliaceae, contains more than 300 species of annual and perennial herbs, worldwide distributed. Several species are used for their biological properties while some are used as food. Species from the genus Valeriana have been used for their antispasmodic, relaxing, and sedative properties, which have been mainly attributed to the presence of valepotriates, borneol derivatives, and isovalerenic acid. Among this genus, the most common and employed species is Valerianaofficinalis. Although valerian has been traditionally used as a mild sedative, research results are still controversial regarding the role of the different active compounds, the herbal preparations, and the dosage used. The present review is designed to summarize and critically describe the current knowledge on the different plant species belonging to Valerianaceae, their phytochemicals, their uses in the treatment of different diseases with particular emphasis on the effects on the central nervous system. The available information on this sub-family was collected from scientific databases up until year 2020. The following electronic databases were used: PubMed, Scopus, Sci Finder, Web of Science, Science Direct, NCBI, and Google Scholar. The search terms used for this review included Valerianaceae, Valeriana, Centranthus, Fedia, Patrinia, Nardostachys, Plectritis, and Valerianella, phytochemical composition, in vivo studies, Central Nervous System, neuroprotective, antidepressant, antinociceptive, anxiolytic, anxiety, preclinical and clinical studies.

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