Nitric oxide mechanism in the protective effect of antidepressants against 3-nitropropionic acid-induced cognitive deficit, glutathione and mitochondrial alterations in animal model of Huntington's disease

Kumar, Puneet; Kalonia, Harikesh; Kumar, Anil

doi:10.1097/fbp.0b013e32833a5bf4

Cited by 43 publications

(26 citation statements)

References 63 publications

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“…Intracellular bacterial killing by neutrophils is primarily mediated via the generation of reactive oxygen species (ROS) and reactive nitrogen species (35,42). The importance of the NADPH oxidase to the host defense is shown by the frequent infections resulting from the impaired killing of microbes in patients with chronic granulomatous disease (CGD) (61).…”

Section: R E T R a C T E Dmentioning

confidence: 99%

NOD2 Signaling Contributes to Host Defense in the Lungs against Escherichia coli Infection

Theivanthiran¹,

Batra²,

Balamayooran³

et al. 2012

Infect Immun

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Bacterial pneumonia remains a significant cause of mortality in the United States. The innate immune response is the first line of defense against invading bacteria. Neutrophil recruitment to the lungs is the first step in a multistep sequence leading to bacterial clearance. Ligand interaction with pattern-recognizing receptors (PRRs) leads to chemokine production, which drives neutrophils to the site of infection. Although we demonstrated that RIP2 is important for host defense in the lungs against Escherichia coli, the individual roles of NOD1 and NOD2 in pulmonary defense have not been addressed. Here, we explored the role of NOD2 in neutrophil-mediated host defense against an extracellular pathogen, E. coli. We found enhanced bacterial burden and reduced neutrophil and cytokine/chemokine levels in the lungs of NOD2 ؊/؊ mice following E. coli infection. Furthermore, we observed reduced activation of NF-B and mitogen-activated protein kinases (MAPKs) in the lungs of NOD2 ؊/؊ mice upon E. coli challenge. Moreover, NOD2؊/؊ neutrophils show impaired intracellular bacterial killing. Using NOD2/RIP2 ؊/؊ mice, we observed bacterial burden and neutrophil accumulation in the lungs similar to those seen with NOD2 ؊/؊ mice. In addition, bone marrow-derived macrophages obtained from NOD2/RIP2؊/؊ mice demonstrate a reduction in activation of NF-B and MAPKs similar to that seen with NOD2 ؊/؊ mice in response to E. coli. These findings unveil a previously unrecognized role of the NOD2-RIP2 axis for host defense against extracellular Gram-negative bacteria. This pathway may represent a novel target for the treatment of lung infection/inflammation.

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Section: R E T R a C T E Dmentioning

confidence: 99%

NOD2 Signaling Contributes to Host Defense in the Lungs against Escherichia coli Infection

Theivanthiran¹,

Batra²,

Balamayooran³

et al. 2012

Infect Immun

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“…Neuronal excitotoxicity is defined as neuronal death arising from prolonged stimulation of NMDA receptor and excessive influx of calcium ions into the cell (Kumar et al 2010;Mehta et al 2013). Striatum receives large glutamatergic input from corticostriatal afferents and is at high risk of glutamate-mediated excitotoxic injury.…”

Section: Discussionmentioning

confidence: 99%

“…Several mechanisms have been proposed in context of HD neuropathology, but neurochemical alteration, excitotoxicity, oxidative stress, mitochondrial dysfunction, neuroinflammation are among the most well-established concepts (Kumar et al 2011;Brouillet 2014). The neuropathological hallmark of HD is selective and immense degradation of GABAergic medium spiny neurons (MSNs) (Kumar et al 2010). The MSNs of striatum contain relatively express high number of N-methyl-D-aspartate (NMDA) receptor and therefore are more prone to excitotoxic cell death.…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Spermidine Against Excitotoxic Neuronal Death Induced by Quinolinic Acid in Rats: Possible Neurotransmitters and Neuroinflammatory Mechanism

et al. 2015

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Huntington disease is hyperkinetic movement disorder characterized by selective and immense degradation of GABAergic medium spiny neurons in striatum. Quinolinic acid (QA)-induced neurotoxicity involves a cascade of events such as excitotoxicity, ATP depletion, oxidative stress, neuroinflammation, as well as selective GABAergic neuronal loss. Therefore, we investigated spermidine, an endogenous molecule with free radical scavenging, anti-inflammatory, and N-methyl-D-aspartate receptor antagonistic properties, for its beneficial potential if any, in QA-induced Huntington's like symptoms in rats. Rats were administered with QA (200 nmol/2 µl saline) bilaterally on 0 day. Spermidine (5 and 10 mg/kg, p.o.) was administered for 21 days once a day. Behavioral parameters (body weight, locomotor activity, grip strength, and narrow beam walk) observations were done on 1st, 7th, 14th, and 21st day after QA treatment. On 21st day, animals were sacrificed and rat striatum was isolated for biochemical (LPO, GSH, Nitrite), neuroinflammation (TNF-α, IL-1β, and IL-6), and neurochemical analysis (GABA, glutamate, dopamine, norepinephrine, serotonin, DOPAC, HVA, 5-HIAA, adenosine, adenine, hypoxanthine, and inosine). QA treatment significantly altered body weight, locomotor activity, motor coordination, oxidative defense (increased LPO, nitrite, and decreased GSH), pro-inflammatory levels (TNF-α, IL-6 and IL-1β), GABA, glutamate, catecholamines level (norepinephrine, dopamine, and serotonin and their metabolites), and purines level (adenosine, inosine, and hypoxanthine). Spermidine (5 and 10 mg/kg, p.o.) significantly attenuated these alterations in body weight, motor impairments, oxidative stress, neuroinflammatory markers, GABA, glutamate, catecholamines, adenosine, and their metabolites levels in striatum. The neuroprotective effect of spermidine against QA-induced excitotoxic cell death is attributed to its antioxidant, N-methyl-D-aspartate receptor antagonistic, anti-inflammatory properties, and prevention of neurotransmitters alteration in striatum.

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“…Hallazgos previos de nuestro grupo, y de otros investigadores, muestran que el ácido 3-nitropropiónico ejerce fundamentalmente su acción sobre el cuerpo estriado, aunque la corteza cerebral y el hipocampo también se ven afectados, pero en menor medida (18,(23)(24)(25)(26)(27)(28).…”

Section: Discussionunclassified

Antioxidant effect of oleic acid and hydroxytyrosol in an experimental model similar to Huntington's disease

Alconchel¹,

Santamarı́a²,

Túnez³

2014

Actual. Med.

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Efecto antioxidante del ácido oleico e hidroxitirosol en un modelo experimental similar a la enfermedad de Huntington ResumenLos radicales libres juegan un papel fundamental en la alteración neuronal que tiene lugar en enfermedades neurodegenerativas y en el envejecimiento cerebral. Se ha asociado la dieta Mediterránea con la reducción del riesgo de padecer enfermedades neurodegenerativas. Objetivos. Este estudio fue diseñado para probar si el ácido oleico y el hidroxitirosol, componentes del aceite de oliva virgen-extra, ejercen un efecto antioxidante protector en el cerebro ante el estrés oxidativo inducido por el ácido 3-nitropropiónico. Métodos. El ácido 3-nitropropiónico se administró intraperitonealmente a una dosis de 20 mg/kg de peso durante cuatro días consecutivos. El ácido oleico (con una dosis del 4% de calorías ingeridas diariamente por el animal) y el hidroxitirosol (2,5 mg/kg de peso en solución acuosa) se administraron durante 14 días a ratas Wistar. Resultados. El ácido 3-nitropropiónico causó un aumento de la peroxidación lipídica y de la actividad de la glutatión peroxidasa, y una reducción en la concentración de glutatión reducido. Los resultados obtenidos además demuestran que el ácido oleico y el hidroxitirosol reducen los niveles de los productos de peroxidación lipídica y bloquean el agotamiento del glutatión reducido en el cerebro tras la administración de ácido 3-nitropropiónico. Conclusión. Tanto el ácido oleico como el hidroxitirosol actúan como potentes antioxidantes frente al estrés oxidativo inducido por el ácido 3-nitropropiónico. AbstractFree radicals play an important role in neuronal alterations during the progression of neurodegenerative disorders and brain aging. Mediterranean-style diet has been associated to a reduction in the risk to develop neurodegenerative disorders. Objectives. This study was designed to test whether oleic acid and hydroxytyrosol, both components of extra-virgin olive oil, exert an antioxidant and protective effect in the brain subjected to oxidative stress induced by 3-nitropropionic acid. Methods. 3-Nitropropionic acid was administered intraperitoneally to animals at a dose of 20 mg/kg for 4 consecutive days. Oleic acid (given at a dose equivalent to 4% of the calories ingested every day per animal) and hydroxytyrosol (2,5 mg/kg, dissolved in aqueoussolution) were administered during 14 consecutive days to Wistar rats. Results. 3-Nitropropionic acid caused increased levels of lipid peroxidation and glutathione peroxidase activity, and a depletion in the concentration of reduced glutathione. Our findings also demonstrate that oleic acid and hydroxytyrosol reduce the levels of lipid peroxidation and prevent the depletion of reduced glutathione in the brain induced by the administration of 3-nitropropionic acid. Conclusion. Both oleic acid and hydroxytyrosol act as potent antioxidants against the oxidative damage induced by 3-nitropropionic acid.

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Nitric oxide mechanism in the protective effect of antidepressants against 3-nitropropionic acid-induced cognitive deficit, glutathione and mitochondrial alterations in animal model of Huntington's disease

Cited by 43 publications

References 63 publications

NOD2 Signaling Contributes to Host Defense in the Lungs against Escherichia coli Infection

NOD2 Signaling Contributes to Host Defense in the Lungs against Escherichia coli Infection

Protective Effect of Spermidine Against Excitotoxic Neuronal Death Induced by Quinolinic Acid in Rats: Possible Neurotransmitters and Neuroinflammatory Mechanism

Antioxidant effect of oleic acid and hydroxytyrosol in an experimental model similar to Huntington's disease

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