Docosahexaenoic acid and tetracyclines as promising neuroprotective compounds with poly(ADP-ribose) polymerase inhibitory activities for oxidative/genotoxic stress treatment

Cieślik, Magdalena; Pyszko, Joanna; Strosznajder, Joanna B.

doi:10.1016/j.neuint.2013.02.016

Cited by 23 publications

(18 citation statements)

References 79 publications

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“…Relevant to this scheme is that DHA co-treatment in a DNA alkylating agent-treated hippocampal cell line blocks PARP-1 activity (PAR formation) while preventing oxidative stress and neuronal death [98]. In view of PET neuroimaging results indicating DHA metabolic deficits in brains of chronic alcoholics [99], our DHA findings in vitro reinforce an implication from that report that n-3 fatty acid supplementation during withdrawal therapy could be beneficial for cognitive support and even neuroprotection.…”

Section: Discussionsupporting

confidence: 65%

Neuroinflammation and Neurodegeneration in Adult Rat Brain from Binge Ethanol Exposure: Abrogation by Docosahexaenoic Acid

et al. 2014

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Evidence that brain edema and aquaporin-4 (AQP4) water channels have roles in experimental binge ethanol-induced neurodegeneration has stimulated interest in swelling/edema-linked neuroinflammatory pathways leading to oxidative stress. We report here that neurotoxic binge ethanol exposure produces comparable significant effects in vivo and in vitro on adult rat brain levels of AQP4 as well as neuroinflammation-linked enzymes: key phospholipase A2 (PLA2) family members and poly (ADP-ribose) polymerase-1 (PARP-1). In adult male rats, repetitive ethanol intoxication (3 gavages/d for 4 d, ∼9 g/kg/d, achieving blood ethanol levels ∼375 mg/dl; “Majchrowicz” model) significantly increased AQP4, Ca+2-dependent PLA2 GIVA (cPLA2), phospho-cPLA2 GIVA (p-cPLA2), secretory PLA2 GIIA (sPLA2) and PARP-1 in regions incurring extensive neurodegeneration in this model—hippocampus, entorhinal cortex, and olfactory bulb—but not in two regions typically lacking neurodamage, frontal cortex and cerebellum. Also, ethanol reduced hippocampal Ca+2-independent PLA2 GVIA (iPLA2) levels and increased brain “oxidative stress footprints” (4-hydroxynonenal-adducted proteins). For in vitro studies, organotypic cultures of rat hippocampal-entorhinocortical slices of adult age (∼60 d) were ethanol-binged (100 mM or ∼450 mg/dl) for 4 d, which augments AQP4 and causes neurodegeneration (Collins et al. 2013). Reproducing the in vivo results, cPLA2, p-cPLA2, sPLA2 and PARP-1 were significantly elevated while iPLA2 was decreased. Furthermore, supplementation with docosahexaenoic acid (DHA; 22:6n-3), known to quell AQP4 and neurodegeneration in ethanol-treated slices, blocked PARP-1 and PLA2 changes while counteracting endogenous DHA reduction and increases in oxidative stress footprints (3-nitrotyrosinated proteins). Notably, the PARP-1 inhibitor PJ-34 suppressed binge ethanol-dependent neurodegeneration, indicating PARP upstream involvement. The results with corresponding models support involvement of AQP4- and PLA2-associated neuroinflammatory pro-oxidative pathways in the neurodamage, with potential regulation by PARP-1 as well. Furthermore, DHA emerges as an effective inhibitor of these binge ethanol-dependent neuroinflammatory pathways as well as associated neurodegeneration in adult-age brain.

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Section: Discussionsupporting

confidence: 65%

Neuroinflammation and Neurodegeneration in Adult Rat Brain from Binge Ethanol Exposure: Abrogation by Docosahexaenoic Acid

et al. 2014

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“…2 and 8); however, this hypothesis needs further investigation. Regarding the participation of inhibition of AIF translocation in neuroprotection mediated by fatty acids, it has been shown that that mechanism is involved in neuroprotective effect of docosahexaenoic acid (DHA, 20 mM), a major dietary v-3 long-chain polyunsaturated fatty acids (PUFA), against oxidative/genotoxic stress induced by MNNG (N-methyl-N 0 -nitro-N-nitrosoguanidine) in neuronal HT-22 cells [Cieslik et al, 2013]. Based on our data and the above-mentioned study, it can be speculated that inhibition of AIF translocation could be a common neuroprotective mechanism mediated by MUFAs and PUFAs.…”

Section: Discussionmentioning

confidence: 99%

An Involvement of PI3‐K/Akt Activation and Inhibition of AIF Translocation in Neuroprotective Effects of Undecylenic Acid (UDA) Against Pro‐Apoptotic Factors‐Induced Cell Death in Human Neuroblastoma SH‐SY5Y Cells

Jantas

Piotrowski

Lasoń

2015

J of Cellular Biochemistry

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Undecylenic acid (UDA), a naturally occurring 11-carbon unsaturated fatty acid, has been used for several years as an economical antifungal agent and a nutritional supplement. Recently, the potential usefulness of UDA as a neuroprotective drug has been suggested based on the ability of this agent to inhibit μ-calpain activity. In order to verify neuroprotective potential of UDA, we tested protective efficacy of this compound against cell damage evoked by pro-apoptotic factors (staurosporine and doxorubicin) and oxidative stress (hydrogen peroxide) in human neuroblastoma SH-SY5Y cells. We showed that UDA partially protected SH-SY5Y cells against the staurosporine- and doxorubicin-evoked cell death; however, this effect was not connected with its influence on caspase-3 activity. UDA decreased the St-induced changes in mitochondrial and cytosolic AIF level, whereas in Dox-model it affected only the cytosolic AIF content. Moreover, UDA (1-40 μM) decreased the hydrogen peroxide-induced cell damage which was connected with attenuation of hydrogen peroxide-mediated necrotic (PI staining, ADP/ATP ratio) and apoptotic (mitochondrial membrane potential, caspase-3 activation, AIF translocation) changes. Finally, we demonstrated that an inhibitor of PI3-K/Akt (LY294002) but not MAPK/ERK1/2 (U0126) pathway blocked the protection mediated by UDA in all tested models of SH-SY5Y cell injury. These in vitro data point to UDA as potentially effective neuroprotectant the utility of which should be further validated in animal studies.

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“…Preparation of the subcellular fraction was performed as described previously by Cieślik et al (2013) [8]. Cells were washed and scraped into ice-cold PBS and were pelleted at 1000 rpm for 3 min at 4ºC.…”

Section: Preparation Of the Subcellular Fractionmentioning

confidence: 99%

Original article The key role of sphingosine kinases in the molecular mechanism of neuronal cell survival and death in an experimental model of Parkinson’s disease

Pyszko¹,

Strosznajder²

2014

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Docosahexaenoic acid and tetracyclines as promising neuroprotective compounds with poly(ADP-ribose) polymerase inhibitory activities for oxidative/genotoxic stress treatment

Cited by 23 publications

References 79 publications

Neuroinflammation and Neurodegeneration in Adult Rat Brain from Binge Ethanol Exposure: Abrogation by Docosahexaenoic Acid

Neuroinflammation and Neurodegeneration in Adult Rat Brain from Binge Ethanol Exposure: Abrogation by Docosahexaenoic Acid

An Involvement of PI3‐K/Akt Activation and Inhibition of AIF Translocation in Neuroprotective Effects of Undecylenic Acid (UDA) Against Pro‐Apoptotic Factors‐Induced Cell Death in Human Neuroblastoma SH‐SY5Y Cells

Original article The key role of sphingosine kinases in the molecular mechanism of neuronal cell survival and death in an experimental model of Parkinson’s disease

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