Corticosterone synthesis inhibitor metyrapone ameliorates chronic hypobaric hypoxia induced memory impairment in rat

Baitharu, Iswar; Deep, Satya Narayan; Jain, Vishal; Barhwal, Kalpana; Malhotra, A. S.; Hota, Sunil Kumar; Prasad, Dipti; Ilavazhagan, G.

doi:10.1016/j.bbr.2011.11.030

Cited by 35 publications

(23 citation statements)

References 62 publications

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“…Recent reports on the differential susceptibility of brain regions to hypoxia suggest that the hippocampus is more vulnerable to HH stress compared with the cortex and striatum because there are more glutaminergic neurons. 10,11 In conditions of HH the nuclear factor kappa B (NF-κB) is a ti ated hi h i reases the expression of hypoxia inducible factor-1 alpha (HIF-1α). 5,12 The HIF-1α a ti ates o er 100 genes involved inclusively in erythropoiesis, angiogenesis, energy metabolism, proliferation/cell survival, apoptosis, etc.…”

Section: Introductionmentioning

confidence: 99%

Quercetin Ameliorate Oxidative/Nitrosative Stress in The Brain of Rats Exposed to Intermittent Hypobaric Hypoxia

Chis

Baltaru²,

Dumitrovici

et al. 2016

Revista Virtual De Química

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http://rvq.sbq.org.br Quercetina na Melhora do Estresse Oxidativo/Nitrosativo no Cérebro de Ratos Expostos a Hipóxia Hipobárica Intermitente Resumo: Exposição à alta altitude é um extremo fisiológico do estresse oxidativo/nitrosativo, onde o cérebro é o tecido mais sensível do corpo. A quercetina (Que) é um flavonóide natural abundante em frutas e legumes. O presente estudo investigou mudanças específicas na região do cérebro do estriado, hipocampo e córtex, sobre marcadores de estresse oxidativo/nitrosativo, e os efeitos da administração de Que em ratos expostos à hipóxia hipobárica intermitente (IHH). Ratos Wistar machos foram expostos a curto prazo (dois dias) ou de longo prazo (4 semanas, 5 dias/semana) à IHH em uma câmara hipobárica. Metade dos ratos receberam Que (30 mg / kg de peso corporal) diariamente, antes de cada exposição à IHH. Os ratos de controle foram mantidos sob condições de normóxia normobárica (Nx), tratando de uma maneira correspondente. Após a última exposição à IHH, o cérebro foi removido e os marcadores de estresse oxidativo/nitrosativo foram determinados nas três partes de tecido homogeneizado do cérebro (estriado, hipocampo e córtex): os radicais livres (malondialdeído, MDA e proteínas carboniladas, CP), nitrito mais nitrato (NOx) produção e atividade de enzimas antioxidantes (superóxido dismutase, SOD, e catalase, CAT). Os resultados indicam um aumento na produção de radicais livres e de NOx, com uma redução do sistema de defesa antioxidante em todas as três regiões do cérebro, após a exposição à IHH. O tratamento com Que reduziu significativamente os radicais livres e produção de NOx e significativamente aumentou os níveis de SOD e CAT em todos as três regiões do cérebro após a exposição à IHH. A observação sugere que a hipóxia afeta diferencialmente as regiões do cérebro, e Que fornece neuroproteção substancial contra danos oxidativo/nitrosativo induzido por IHH.

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Section: Introductionmentioning

confidence: 99%

Quercetin Ameliorate Oxidative/Nitrosative Stress in The Brain of Rats Exposed to Intermittent Hypobaric Hypoxia

Chis

Baltaru²,

Dumitrovici

et al. 2016

Revista Virtual De Química

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“…Hypothalamic corticosteroid releasing factor overexpression contributes to HPA axis hyperactivity in psychiatric patients [13]. Persistent elevation in corticosterone level following prolonged exposure to HH leads to augmented neurodegeneration and memory impairment [14,15]. Apart from HPA axis hyperactivity, altered glutamatergic neurotransmission has been a major pathological factor in depression and glutamatergic agents have demonstrated rapid and robust antidepressant activity in humans.…”

Section: Introductionmentioning

confidence: 99%

“…Since forced swim test requires the rats to keep on swimming actively for five minutes, it makes the rats more exhausted. However, exposure to HH for 7 days has been reported to induce mitochondrial dysfunction and compromised neuronal energetic due to reduced availability of glucose as a result of hypoxia induced hypophagia [14]. Prolonged exposure for 21 days onset acclimatization to HH and increased food intake resulting in improved the neuronal energy status.…”

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confidence: 99%

Exposure to Hypobaric Hypoxia and Reoxygenation Induces Transient Anxiety-Like Behavior in Rat

Baitharu¹,

Jain²,

Deep³

et al. 2013

JBBS

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Chronic exposure to hypobaric hypoxia (HH) causes memory impairment and prolonged state of mental confusion. However, effect of high altitude exposure on mood state and its underlying mechanisms have been poorly studied. Present study was undertaken to investigate the mood state alteration following chronic exposure to HH. Male Sprague Dawley rats were divided into five groups and exposed to hypoxia for 3, 7, 14 and 21 days in an animal decompression chamber at an altitude of 25,000ft. Anxiety-and depression-like behaviors were assessed by using various mazes along with changes in serotonin and glutamate level. Our study revealed a decrease in exploratory, grooming and rearing behavior in open field test following initial exposure to HH for 7 days without affecting the locomotory behavior. Initial exposure to HH-decreased time spent in open arm of elevated plus maze indicating induction of anxiety-like behavior which normalized on prolonged hypoxic exposure for 21 days. Hypoxic exposure for 7 days induced anhedonia and increased despair behavior in rat while there was steady improvement in these behaviors when exposed for 21 days. Decrease in serotonin level was noted in hippocampus along with elevated corticosterone and glutamate level which gradually decreased on prolonged exposure to HH. These findings suggest that initial exposure to HH increases transient anxiety-like behavior in rats followed by gradual improvement in mood state on prolonged exposure. Further, the study also indicates the involvement of serotonergic system in mood state alteration at high altitude following chronic exposure and reoxygenation.

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“…Current studies have indicated the potential of met to block deleterious effects on the lung (Baitharu et al . ; Paek et al . ) through neuroprotective action (Baitharu et al .…”

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confidence: 99%

“…The effects of met on surfactant, oxidative stress (Sosenko et al 1986) and pro-inflammatory cytokines (Peruzzo et al 2010) have been analysed. Current studies have indicated the potential of met to block deleterious effects on the lung (Baitharu et al 2012;Paek et al 2014) through neuroprotective action (Baitharu et al 2012).…”

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confidence: 99%

Inhibition of endogenous glucocorticoid synthesis aggravates lung injury triggered by septic shock in rats

Incerpi

Oliveira²,

Pereira

et al. 2015

Int J Experimental Path

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The aim of this study was to determine the effects of previous administration of metyrapone (met) on the acute lung injury (ALI) induced by caecal ligation and puncture (CLP) and to explore met's relationship with endogenous glucocorticoids (GCs) as measured by inflammatory, oxidative and functional parameters. One hundred and thirty-five Wistar rats were divided into three main groups: Control (Naïve), Sham and CLP. The animals received pretreatment one hour before surgery. The Naïve group did not undergo any procedure or pretreatment. The Sham group only had the caecum exposed and was pretreated with saline. The CLP group was divided into three pretreatments: metyrapone (CLP met 50 mg/kg i.p.), dexamethasone (CLP dex 0.5 mg/kg i.p.) or saline (CLP sal equivalent volume of 0.9% NaCl). Analyses were performed after 6 and 24 h of sepsis. Previous administration of met significantly increased inflammatory cells, as well as myeloperoxidase (MPO) activity in the lung tissue and alveolar collapsed area, with consequent impairment of respiratory mechanics being observed compared to Sham and Naïve; CLP sal exhibited similar results to those of met. The met reduced corticosterone (CCT) levels and dramatically increased hydrogen peroxide (H2 O2 ) levels in the lung tissue compared to CLP sal. Our results suggest that previous administration of met may have contributed to increased pulmonary oxidative stress and increased mortality by mechanisms dependent of endogenous GC.

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Corticosterone synthesis inhibitor metyrapone ameliorates chronic hypobaric hypoxia induced memory impairment in rat

Cited by 35 publications

References 62 publications

Quercetin Ameliorate Oxidative/Nitrosative Stress in The Brain of Rats Exposed to Intermittent Hypobaric Hypoxia

Quercetin Ameliorate Oxidative/Nitrosative Stress in The Brain of Rats Exposed to Intermittent Hypobaric Hypoxia

Exposure to Hypobaric Hypoxia and Reoxygenation Induces Transient Anxiety-Like Behavior in Rat

Inhibition of endogenous glucocorticoid synthesis aggravates lung injury triggered by septic shock in rats

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