# Neuroprotection by Cocktails of Dietary Antioxidants under Conditions of Nerve Growth Factor Deprivation

**Authors:** Flavio Amara, Miluscia Berbenni, Martina Fragni, Giampaolo Leoni, Sandra Viggiani, Vita Maria Ippolito, Marilena Larocca, Rocco Rossano, Lilia Alberghina, Paolo Riccio, Anna Maria Colangelo

PMC · DOI: 10.1155/2015/217258 · Oxidative Medicine and Cellular Longevity · 2015-07-08

## TL;DR

This study shows that combinations of dietary antioxidants can protect neurons from damage caused by a lack of nerve growth factor, potentially offering a strategy to combat neurodegenerative diseases.

## Contribution

The study introduces the efficacy of antioxidant cocktails at low concentrations in protecting neurons under NGF deprivation.

## Key findings

- Antioxidants reduced ROS levels and preserved mitochondrial function in PC12 cells during NGF deprivation.
- Defined antioxidant cocktails at low concentrations provided neuroprotection similar to higher single-antioxidant doses.
- Low-concentration antioxidant cocktails may reduce oxidative damage in neurodegenerative diseases with fewer side effects.

## Abstract

Dietary antioxidants may be useful in counteracting the chronic inflammatory status in neurodegenerative diseases by reducing oxidative stress due to accumulation of reactive oxygen species (ROS). In this study, we newly described the efficacy of a number of dietary antioxidants (polyphenols, carotenoids, thiolic compounds, and oligoelements) on viability of neuronal PC12 cells following Nerve Growth Factor (NGF) deprivation, a model of age-related decrease of neurotrophic support that triggers neuronal loss. Neuroprotection by antioxidants during NGF deprivation for 24 h was largely dependent on their concentrations: all dietary antioxidants were able to efficiently support cell viability by reducing ROS levels and restoring mitochondrial function, while preserving the neuronal morphology. Moreover, ROS reduction and neuroprotection during NGF withdrawal were also achieved with defined cocktails of 3–6 different antioxidants at concentrations 5–60 times lower than those used in single treatments, suggesting that their antioxidant activity was preserved also at very low concentrations. Overall, these data indicate the beneficial effects of antioxidants against oxidative stress induced by decreased NGF availability and suggest that defined cocktails of dietary factors at low concentrations might be a suitable strategy to reduce oxidative damage in neurodegenerative diseases, while limiting possible side effects.

## Linked entities

- **Chemicals:** carotenoids (PubChem CID 11227325)

## Full-text entities

- **Genes:** Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}, Ngf (nerve growth factor) [NCBI Gene 18049] {aka Ngfb, beta-NGF}, App (amyloid beta precursor protein) [NCBI Gene 54226] {aka Abeta}, Calcr (calcitonin receptor) [NCBI Gene 116506], Ppara (peroxisome proliferator activated receptor alpha) [NCBI Gene 25747] {aka PPAR}, Hmox1 (heme oxygenase 1) [NCBI Gene 24451] {aka HEOXG, Heox, Hmox, Ho-1, Ho1, hsp32}, Ppargc1a (PPARG coactivator 1 alpha) [NCBI Gene 83516] {aka LRPGC1, PGC-1v, PGCvf, PGCvf-1, PGCvf1, Ppargc1}, NGF (nerve growth factor) [NCBI Gene 4803] {aka Beta-NGF, HSAN5, NGFB}, Ngf (nerve growth factor) [NCBI Gene 310738] {aka Ngfb, beta-NGF}, Snca (synuclein alpha) [NCBI Gene 29219], Sod1 (superoxide dismutase 1) [NCBI Gene 24786] {aka CuZnSOD}, App (amyloid beta precursor protein) [NCBI Gene 11820] {aka Abeta, Abpp, Adap, Ag, Cvap, E030013M08Rik}, Bcl2 (BCL2, apoptosis regulator) [NCBI Gene 24224] {aka Bcl-2}, Tubb3 (tubulin, beta 3 class III) [NCBI Gene 22152] {aka 3200002H15Rik, M(beta)3, M(beta)6}, Ngfr (nerve growth factor receptor) [NCBI Gene 24596] {aka LNGFR, RNNGFRR, Tnfrsf16, p75, p75NTR}, IFNB1 (interferon beta 1) [NCBI Gene 3456] {aka IFB, IFF, IFN-beta, IFNB}, CALCR (calcitonin receptor) [NCBI Gene 799] {aka CRT, CT-R, CTR, CTR1}, Ntrk1 (neurotrophic receptor tyrosine kinase 1) [NCBI Gene 59109] {aka Trk}, Akt1 (AKT serine/threonine kinase 1) [NCBI Gene 24185] {aka Akt}, Nfe2l2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 83619]
- **Diseases:** Mitochondrial Dysfunction (MESH:D028361), PD (MESH:D010300), Autoimmune Encephalomyelitis (MESH:D004681), ischemia (MESH:D007511), cognitive dysfunction (MESH:D003072), ALS (MESH:D000690), Dysfunctional mitochondria (MESH:C564971), neuronal dysfunction (MESH:D009461), neurotoxicity (MESH:D020258), cancer (MESH:D009369), AD (MESH:D000544), hypertension (MESH:D006973), MS (MESH:D009103), cardiovascular disease (MESH:D002318), toxic (MESH:D064420), neuronal death (MESH:D009410), glucose (MESH:D018149), chronic inflammatory diseases (MESH:D002908), age- (MESH:D019588), inflammation (MESH:D007249), cardiovascular and neurodegenerative diseases (MESH:D019636)
- **Chemicals:** HS (MESH:D006859), N-Acetylcysteine (MESH:D000111), 2',7'-Dichlorodihydrofluorescein-diacetate (MESH:C110400), carotenoids (MESH:D002338), 6-hydroxydopamine (MESH:D016627), ATP (MESH:D000255), PBS (MESH:D007854), Polyphenols (MESH:D059808), 2',7'-dichlorofluorescein (MESH:C037631), E (MESH:D004540), CRC (MESH:D003474), LYC (-), ALA (MESH:D000409), L-glutamine (MESH:D005973), DCF (MESH:D015649), GTE (MESH:C045651), oxygen (MESH:D010100), saturated fatty acids (MESH:D005227), G418 (MESH:C010680), formazan (MESH:D005562), Triton X-100 (MESH:D017830), paraformaldehyde (MESH:C003043), catechins (MESH:D002392), flavonoids (MESH:D005419), vitamin C (MESH:D001205), transfatty acids (MESH:D044242), 2',7'-dichlorofluorescein-diacetate (MESH:C029569), tetrazolium salts (MESH:D013778), ROS (MESH:D017382), CO2 (MESH:D002245), thiol (MESH:D013438), ALA (MESH:D008063), sugars (MESH:D000073893), streptomycin (MESH:D013307), MPTP (MESH:D015632), lipids (MESH:D008055), free radicals (MESH:D005609), glucoside (MESH:D005960), MTT (MESH:C070243), Sel (MESH:D012643), RSV (MESH:D000077185), 4,6-diamidino-2-phenylindole (MESH:C007293), hydroxytyrosol (MESH:C005975), ALCAR (MESH:D000108), penicillin (MESH:D010406), LYC (MESH:D000077276), CoQ (MESH:C024989), glutathione (MESH:D005978), QRC (MESH:D011794),  (MESH:D020932),  (MESH:D000975)
- **Species:** Homo sapiens (human, species) [taxon 9606], Solanum lycopersicum (tomato, species) [taxon 4081], Mus musculus (house mouse, species) [taxon 10090], water melon [taxon 260674], Rattus norvegicus (brown rat, species) [taxon 10116]
- **Cell lines:** PC12 — Rattus norvegicus (Rat), Rat adrenal gland pheochromocytoma, Cancer cell line (CVCL_0481)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC4510258/full.md

## References

52 references — full list in the complete paper: https://tomesphere.com/paper/PMC4510258/full.md

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Source: https://tomesphere.com/paper/PMC4510258