Quercetin as a prophylactic measure against high altitude cerebral edema

Patir, Himadri; Sarada, S.K.S; Singh, Surender; Mathew, T. Lazar; Singh, Bhagwat; Bansal, Anju

doi:10.1016/j.freeradbiomed.2012.06.010

Cited by 51 publications

(21 citation statements)

References 53 publications

(52 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Quercetin is one of the most important flavonoid known for its antiinflammatory and neuroprotective properties, which can be used as a potent drug against high altitude cerebral edema, because it efficiently attenuates inflammation and cerebral edema formation. 41 Decrease in total brain weight after Quercetin administration and 4 weeks of exposure to IHH we interpreted in this way due to anti-inflammatory and antiedematous effects 24,41 of this flavonoid, but also because of its ability to pass blood brain barrier (BBB) and inhibitory effect of metalloproteinases (MMPs) enzyme activities. 42 The pathological effects of MMPs include hemorrhage, edema, inflammation, BBB breakdown and neurovascular matrix degradation.…”

Section: Discussionmentioning

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

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

View full text Add to dashboard Cite

show abstract

“…Tetrahydroxystilbene glucoside from Polygonum multiforum has protected neurons from cerebral ischemia by activating SIRT1 and inhibiting NF κ B signaling pathway in neurons [58]. Quercetin administration has also protected rat brain against oxidative stress and hypoxia-induced damage through NF κ B inhibition [106]. Similarly, catechin hydrate and fisetin have been shown to protect rat brain against ischemic injury and oxidative damage by inhibiting expression of NF κ B and proinflammatory cytokines such as IL-1 β and TNF- α [83, 94].…”

Section: Polyphenols and Signal Transduction Pathwaysmentioning

confidence: 99%

Polyphenols: Multipotent Therapeutic Agents in Neurodegenerative Diseases

Bhullar

Rupasinghe

2013

Oxidative Medicine and Cellular Longevity

350

194

View full text Add to dashboard Cite

Aging leads to numerous transitions in brain physiology including synaptic dysfunction and disturbances in cognition and memory. With a few clinically relevant drugs, a substantial portion of aging population at risk for age-related neurodegenerative disorders require nutritional intervention. Dietary intake of polyphenols is known to attenuate oxidative stress and reduce the risk for related neurodegenerative diseases such as Alzheimer's disease (AD), stroke, multiple sclerosis (MS), Parkinson's disease (PD), and Huntington's disease (HD). Polyphenols exhibit strong potential to address the etiology of neurological disorders as they attenuate their complex physiology by modulating several therapeutic targets at once. Firstly, we review the advances in the therapeutic role of polyphenols in cell and animal models of AD, PD, MS, and HD and activation of drug targets for controlling pathological manifestations. Secondly, we present principle pathways in which polyphenol intake translates into therapeutic outcomes. In particular, signaling pathways like PPAR, Nrf2, STAT, HIF, and MAPK along with modulation of immune response by polyphenols are discussed. Although current polyphenol researches have limited impact on clinical practice, they have strong evidence and testable hypothesis to contribute clinical advances and drug discovery towards age-related neurological disorders.

show abstract

“…Thus, the mechanisms remain elusive, and effective strategies for prevention or therapy of HACE are presently limited. However, it has been suggested that infection-elicited inflammation is a trigger for HACE [ 3 , 4 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Systemic pro-inflammatory response facilitates the development of cerebral edema during short hypoxia

Song

Gao

et al. 2016

J Neuroinflammation

111

View full text Add to dashboard Cite

BackgroundHigh-altitude cerebral edema (HACE) is the severe type of acute mountain sickness (AMS) and life threatening. A subclinical inflammation has been speculated, but the exact mechanisms underlying the HACE are not fully understood.MethodsHuman volunteers ascended to high altitude (3860 m, 2 days), and rats were exposed to hypoxia in a hypobaric chamber (5000 m, 2 days). Human acute mountain sickness was evaluated by the Lake Louise Score (LLS), and plasma corticotrophin-releasing hormone (CRH) and cytokines TNF-α, IL-1β, and IL-6 were measured in rats and humans. Subsequently, rats were pre-treated with lipopolysaccharide (LPS, intraperitoneal (ip) 4 mg/kg, 11 h) to induce inflammation prior to 1 h hypoxia (7000 m elevation). TNF-α, IL-1β, IL-6, nitric oxide (NO), CRH, and aquaporin-4 (AQP4) and their gene expression, Evans blue, Na+-K+-ATPase activity, p65 translocation, and cell swelling were measured in brain by ELISA, Western blotting, Q-PCR, RT-PCR, immunohistochemistry, and transmission electron micrography. MAPKs, NF-κB pathway, and water permeability of primary astrocytes were demonstrated. All measurements were performed with or without LPS challenge. The release of NO, TNF-α, and IL-6 in cultured primary microglia by CRH stimulation with or without PDTC (NF-κB inhibitor) or CP154,526 (CRHR1 antagonist) were measured.ResultsHypobaric hypoxia enhanced plasma TNF-α, IL-1β, and IL-6 and CRH levels in human and rats, which positively correlated with AMS. A single LPS injection (ip, 4 mg/kg, 12 h) into rats increased TNF-α and IL-1β levels in the serum and cortex, and AQP4 and AQP4 mRNA expression in cortex and astrocytes, and astrocyte water permeability but did not cause brain edema. However, LPS treatment 11 h prior to 1 h hypoxia (elevation, 7000 m) challenge caused cerebral edema, which was associated with activation of NF-κB and MAPKs, hypoxia-reduced Na+-K+-ATPase activity and blood-brain barrier (BBB) disruption. Both LPS and CRH stimulated TNF-α, IL-6, and NO release in cultured rat microglia via NF-κB and cAMP/PKA.ConclusionsPreexisting systemic inflammation plus a short severe hypoxia elicits cerebral edema through upregulated AQP4 and water permeability by TLR4 and CRH/CRHR1 signaling. This study revealed that both infection and hypoxia can cause inflammatory response in the brain. Systemic inflammation can facilitate onset of hypoxic cerebral edema through interaction of astrocyte and microglia by activation of TLR4 and CRH/CRHR1 signaling. Anti-inflammatory agents and CRHR1 antagonist may be useful for prevention and treatment of AMS and HACE.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0528-4) contains supplementary material, which is available to authorized users.

show abstract

Quercetin as a prophylactic measure against high altitude cerebral edema

Cited by 51 publications

References 53 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

Polyphenols: Multipotent Therapeutic Agents in Neurodegenerative Diseases

Systemic pro-inflammatory response facilitates the development of cerebral edema during short hypoxia

Contact Info

Product

Resources

About