Nrf2-induced antioxidant protection: A promising target to counteract ROS-mediated damage in neurodegenerative disease?

Vries, Helga E. de; Witte, Maarten E.; Hondius, David; Rozemüller, Annemieke; Drukarch, Benjamin; Hoozemans, Jeroen J. M.; Horssen, Jack van

doi:10.1016/j.freeradbiomed.2008.09.001

Cited by 380 publications

(275 citation statements)

References 191 publications

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“…A proteína Keap1 contém resíduos conservados de cisteína, os quais desempenham um papel crí-tico na manutenção do Nrf2 no citoplasma. Entretanto, um aumento na produção de EROS no organismo promove no citoplasma a dissociação desse complexo, fazendo com que o Nrf2 fique ativado, sendo transportado para o núcleo (34,35). No núcleo das células, esse fator de transcrição se liga a elementos de resposta a antioxidantes (ARE) na região promotora dos genes que transcrevem enzimas antioxidantes endógenas.…”

Section: Discussionunclassified

Efeito da estreptozotocina sobre os perfis glicêmico e lipídico e o estresse oxidativo em hamsters

Silva

Lima

Pedrosa

2011

Arq Bras Endocrinol Metab

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RESUMOObjetivo: Este estudo avaliou os efeitos da estreptozotocina nos perfis glicêmico e lipídico e marcadores de estresse oxidativo em hamsteres. Materiais e métodos: Hamsteres machos Golden Syrian foram divididos em dois grupos: grupo diabético (D), que recebeu uma única injeção de estreptozotocina (STZ -50 mg/kg), e grupo controle (C), que recebeu injeção de tampão citrato. Os animais foram eutanasiados após 10 dias de experimento e o sangue, o fígado e rins foram coletados. Resultados: O grupo diabético apresentou níveis maiores de glicose, triacilgliceróis e colesterol séricos e maior concentração de substâncias reativas ao ácido tiobarbitúrico (TBARs) no fígado e nos rins. Também apresentou significativo aumento da concentração de glutationa no fígado e menores atividades da paraoxonase e do superóxido dismutase. Conclusão: Hamsteres fornecem um bom modelo para o diabetes melito do tipo I e estresse oxidativo, similar ao da síndrome humana, e poderão ser adequados para a análise de compostos antidiabéticos. Arq Bras Endocrinol Metab. 2011;55(1):46-53 Descritores Hamsteres; estreptozotocina; estresse oxidativo; antioxidantes ABSTRACT Objective: This study evaluated the effects of streptozotocin on glycemic and lipid profiles and oxidative stress status in hamsters. Materials and methods: Male Golden Syrian hamsters were divided in diabetic group (D) which received a streptozotocin single injection (STZ -50 mg/kg), and control group (C) which received a single injection of the vehicle citrate buffer. Animals were euthanized after 10 days of experiment and blood, liver and kidneys were collected. Results: The diabetic group had higher levels of glucose, triacylglycerols and cholesterol in serum and thiobarbituric acid reactive substances (TBARS) concentration increased in the liver and kidneys. Diabetes induced a significant increase in glutathione concentration in the liver and decreased paraoxonase and superoxide dismutase activities. Conclusion: Hamsters provide a novel animal model for diabetes mellitus and oxidative stress, similar to the human syndrome, which may be suitable for the testing of antidiabetic compounds. Arq Bras Endocrinol Metab. 2011;55 (1) InTRODUçãO O termo diabetes melito (DM) é uma desordem metabólica de múltiplas etiologias caracterizadas por hiperglicemia crônica com distúrbios no metabolismo de carboidratos, lipídios e proteínas, como resultado do defeito na secreção de insulina ou em sua ação ou ambos (1). Há mais de 250 milhões de pessoas em todo o mundo com diabetes e estima-se que a cada 5 segundos surja um novo caso (2). O diabetes pode gerar complicações como retinopatias, nefropatias, neuropatias e distúrbios endócrinos. O papel do estresse oxidativo nessas complicações tem sido alvo de muito interesse (3,4).

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Section: Discussionunclassified

Efeito da estreptozotocina sobre os perfis glicêmico e lipídico e o estresse oxidativo em hamsters

Silva

Lima

Pedrosa

2011

Arq Bras Endocrinol Metab

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“…With the causal link of oxidative stress with insulin reJanuary 15, 2012|Volume 3|Issue 1| WJD|www.wjgnet.com 23 sistance [15,66] , it is reasonable to expect that Nrf2 activation can be the potential drug target for diabetes treatment [67][68][69][70][71] . Based on existing studies, several aspects of Nrf2 activation can benefit diabetic patients: (1) Nrf2 activation protects pancreatic β-cells from damage [65] and subsequently prevents the onset of diabetes; (2) The sensitizing action of Nrf2 on insulin may bring benefit for diabetic patients with better glucose control; (3) In addition, hyperglycemia-induced endothelial dysfunction, vascular complications and cardiomyocyte damage [72,73] may be prevented by Nrf2 activation by reducing oxidative stress [74][75][76][77] ; and (4) A protective role of the Nrf2 system in diabetic nephropathy and neuropathy is another potential function for a Nrf2 modulating drug [78][79][80][81] .…”

Section: Nrf2 System As a Potential Drug Target For Diabetes Treatmentmentioning

confidence: 99%

Role of nuclear factor (erythroid-derived 2)-like 2 in metabolic homeostasis and insulin action: A novel opportunity for diabetes treatment?

Zhong

Li²,

Liu³

et al. 2012

WJD

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Redox balance is fundamentally important for physiological homeostasis. Pathological factors that disturb this dedicated balance may result in oxidative stress, leading to the development or aggravation of a variety of diseases, including diabetes mellitus, cardiovascular diseases, metabolic syndrome as well as inflammation, aging and cancer. Thus, the capacity of endogenous free radical clearance can be of patho-physiological importance; in this regard, the major reactive oxygen species defense machinery, the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) system needs to be precisely modulated in response to pathological alterations. While oxidative stress is among the early events that lead to the development of insulin resistance, the activation of Nrf2 scavenging capacity leads to insulin sensitization. Furthermore, Nrf2 is evidently involved in regulating lipid metabolism. Here we summarize recent findings that link the Nrf2 system to metabolic homeostasis and insulin action and present our view that Nrf2 may serve as a novel drug target for diabetes and its complications.

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“…The enzyme Lipoxygenase is associated with the production of leukotrienes, which are associated with inflammation of brain tissue mediated by the innate immune system [28]. In the cycle of neuroinflammation and oxidative stress in the central nervous system, iNOS plays a critical role exacerbating the hypoxic environment through overproduction of nitric oxide (NO).…”

Section: Discussionmentioning

confidence: 99%

Dynamic molecular monitoring of retina inflammation byin vivoRaman spectroscopy coupled with multivariate analysis

Marro

Taubes

Abernathy

et al. 2013

Journal of Biophotonics

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Retinal tissue is damaged during inflammation in Multiple Sclerosis. We assessed molecular changes in inflamed murine retinal cultures by Raman spectroscopy. Partial Least Squares‐Discriminant analysis (PLS‐DA) was able to classify retina cultures as inflamed with high accuracy. Using Multivariate Curve Resolution (MCR) analysis, we deconvolved 6 molecular components suffering dynamic changes along inflammatory process. Those include the increase of immune mediators (Lipoxygenase, iNOS and TNFα), changes in molecules involved in energy production (Cytochrome C, phenylalanine and NADH/NAD+) and decrease of Phosphatidylcholine. Raman spectroscopy combined with multivariate analysis allows monitoring the evolution of retina inflammation.Raman spectroscopy analysis of the Retinal Ganglion Cell layer of the retina. (A) Design of the analysis of the Ganglion cell layer (GCL) and Retinal Nerve Fiber Layer (RNFL) of the retina based in the physical properties of laser light and anatomical structure of retinal layers. (B) Examples of raw Raman spectra from representative retina sample after 10 hours incubation time (black) and LPS treated retina sample after 10 hours incubation time (red) and 12 hours incubation time (blue). (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

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Nrf2-induced antioxidant protection: A promising target to counteract ROS-mediated damage in neurodegenerative disease?

Cited by 380 publications

References 191 publications

Efeito da estreptozotocina sobre os perfis glicêmico e lipídico e o estresse oxidativo em hamsters

Efeito da estreptozotocina sobre os perfis glicêmico e lipídico e o estresse oxidativo em hamsters

Role of nuclear factor (erythroid-derived 2)-like 2 in metabolic homeostasis and insulin action: A novel opportunity for diabetes treatment?

Dynamic molecular monitoring of retina inflammation byin vivoRaman spectroscopy coupled with multivariate analysis

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