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Neuroprotective Effects of Pregnenolone Against Oxidative Damage in a 6-Hydroxyd opamine-Induced Parkinson’s Disease Cell Model Using SH-SY5Y Cell Line

Year 2023, Volume: 3 Issue: 4, 74 - 77, 09.10.2023

Abstract

Objective: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons, leading to motor impairments and cognitive deficits. Despite advances in understanding PD’s pathophysiology, effective therapeutic interventions are limited. Oxidative stress, resulting from the overproduction of reactive oxygen and nitrogen species, plays a crucial role in PD progression. Neurosteroids, naturally occurring brain steroids, have been implicated in dopamine signaling regulation and are disrupted in PD. Pregnenolone (Prgn), a neurosteroid, has shown potential neuroprotective properties and antioxidant effects.

Methods: In this study, we investigated the neuroprotective potential of Prgn in an in vitro PD model using SH-SY5Y cells treated with 6-hydroxydopamine (6-OHDA). Pregnenolone pretreatment significantly improved cell viability and reduced oxidative stress induced by 6-OHDA exposure. Moreover, Prgn treatment led to the modulation of antioxidative biomarkers, restoring cellular redox balance.

Results: Our findings suggest that Prgn exerts neuroprotective effects against 6-OHDA-induced neurotoxicity in SH-SY5Y cells by reducing oxidative stress and enhancing cell survival. These results support the exploration of Prgn as a potential therapeutic agent for mitigating PD progression.

Conclusion: In conclusion, our study demonstrates that Prgn, a neurosteroid, exhibits promising neuroprotective effects in an in vitro model of PD by attenuating 6-OHDA-induced oxidative damage and preserving the viability and functional integrity of SH-SY5Y cells.

Ethical Statement

Ethical approval was not required as this study was conducted using a commercially acquired cell line.

References

  • 1. Chmielarz P, Saarma M. Neurotrophic factors for disease-modifying treatments of Parkinson’s disease: gaps between basic science and clinical studies. Pharmacol Rep. October 2020;72(5):1195-1217.
  • 2. Bhatt R, Vaishnav D, Airao V, et al. Neuroprotective potential of saroglitazar in 6-OHDA induced Parkinson’s disease in rats. Chem Biol Drug Des. July 30 2023.
  • 3. Camicioli RM, Colosimo C. Neuropsychiatric symptoms and Parkinson disease: are we looking carefully enough? Neurology. 2023.
  • 4. Ferah Okkay I, Okkay U, Cicek B, et al. Neuroprotective effect of bromelain in 6-hydroxydopamine induced in vitro model of Parkinson’s disease. Mol Biol Rep. 2021;48(12):7711-7717.
  • 5. Ashok A, Andrabi SS, Mansoor S, Kuang Y, Kwon BK, Labhasetwar V. Antioxidant therapy in oxidative stress-induced neurodegenerative diseases: role of nanoparticle-based drug delivery systems in clinical translation. Antioxidants (Basel). 2022;11(2)
  • 6. Frye CA. Neurosteroids’ effects and mechanisms for social, cognitive, emotional, and physical functions. Psych oneur oendo crino logy. 2009;34(suppl 1):S143-S161.
  • 7. Chang KH, Chen CM. The role of oxidative stress in Parkinson’s disease. Antioxidants (Basel). 2020;9(7)
  • 8. Borowicz KK, Piskorska B, Banach M, Czuczwar SJ. Neuroprotective actions of neurosteroids. Front Endocrinol (Lausanne). 2011;2:50.
  • 9. Smith CC, Gibbs TT, Farb DH. Pregnenolone sulfate as a modulator of synaptic plasticity. Psychopharmacology. 2014;231(17):3537-3556.
  • 10. Morsy MA, Abdel-Gaber SA, Mokhemer SA, et al. Pregnenolone inhibits doxorubicin-induced cardiac oxidative stress, inflammation, and apoptosis-role of matrix metalloproteinase 2 and NADPH oxidase 1. Pharmaceuticals (Basel). 2023;16(5)
  • 11. Zhi SM, Fang GX, Xie XM, et al. Melatonin reduces OGD/R-induced neuron injury by regulating redox /infl ammat ion/a popto sis signaling. Eur Rev Med Pharmacol Sci. 2020;24(3):1524-1536.
  • 12. Okkay U, Ferah Okkay I, Aydin IC, et al. Effects of Achillea millefolium on cisplatin induced ocular toxicity: an experimental study. Cutan Ocul Toxicol. 2021;40(3):214-220.
  • 13. Ferah Okkay I, Okkay U, Aydin IC, et al. Centella asiatica extract protects against cisplatin-induced hepatotoxicity via targeting oxidative stress, inflammation, and apoptosis. Environ Sci Pollut Res Int. 2022;29(22):33774-33784.
  • 14. Ferah Okkay I, Okkay U, Gundogdu OL, et al. Syringic acid protects against thioacetamide-induced hepatic encephalopathy: behavioral, biochemical, and molecular evidence. Neurosci Lett. 2022;769: 136385.
  • 15. Okkay U, Ferah Okkay I, Cicek B, Aydin IC, Ozkaraca M. Hepatoprotective and neuroprotective effect of taxifolin on hepatic encephalopathy in rats. Metab Brain Dis. 2022;37(5):1541-1556.
  • 16. Campagnolo M, Emmi A, Biundo R, et al. The pharmacological management of the behavioral aspects of Parkinson’s disease: an update. Expert Opin Pharmacother. 2023:1-9.
  • 17. Feng Mj, Zhang L, Liu Z, Zhou P, Lu X. The expression and release of Hsp60 in 6-OHDA induced in vivo and in vitro models of Parkinson’s disease. Neurochem Res. 2013;38(10):2180-2189.
  • 18. Ferlazzo N, Cirmi S, Maugeri A, et al. Neuroprotective effect of bergamot juice in 6-OHDA-induced SH-SY5Y cell death, an in vitro model of Parkinson’s disease. Pharmaceutics. 2020;12(4)
  • 19. Li Q, Li S, Fang J, et al. Artemisinin confers neuroprotection against 6-OHDA-induced neuronal injury in vitro and in vivo through activation of the ERK1/2 pathway. Molecules. 2023;28(14)
  • 20. Kovalevich J, Langford D. Considerations for the use of SH-SY5Y neuroblastoma cells in neurobiology. Methods Mol Biol. 2013;1078:9-21.
  • 21. Singh A, Kukreti R, Saso L, Kukreti S. Oxidative stress: A key modulator in neurodegenerative diseases. Molecules. 2019;24(8)

Neuroprotective Effects of Pregnenolone Against Oxidative Damage in a 6-Hydroxyd opamine-Induced Parkinson’s Disease Cell Model Using SH-SY5Y Cell Line

Year 2023, Volume: 3 Issue: 4, 74 - 77, 09.10.2023

Abstract

Objective: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons, leading to motor impairments and cognitive deficits. Despite advances in understanding PD’s pathophysiology, effective therapeutic interventions are limited. Oxidative stress, resulting from the overproduction of reactive oxygen and nitrogen species, plays a crucial role in PD progression. Neurosteroids, naturally occurring brain steroids, have been implicated in dopamine signaling regulation and are disrupted in PD. Pregnenolone (Prgn), a neurosteroid, has shown potential neuroprotective properties and antioxidant effects.

Methods: In this study, we investigated the neuroprotective potential of Prgn in an in vitro PD model using SH-SY5Y cells treated with 6-hydroxydopamine (6-OHDA). Pregnenolone pretreatment significantly improved cell viability and reduced oxidative stress induced by 6-OHDA exposure. Moreover, Prgn treatment led to the modulation of antioxidative biomarkers, restoring cellular redox balance.

Results: Our findings suggest that Prgn exerts neuroprotective effects against 6-OHDA-induced neurotoxicity in SH-SY5Y cells by reducing oxidative stress and enhancing cell survival. These results support the exploration of Prgn as a potential therapeutic agent for mitigating PD progression.

Conclusion: In conclusion, our study demonstrates that Prgn, a neurosteroid, exhibits promising neuroprotective effects in an in vitro model of PD by attenuating 6-OHDA-induced oxidative damage and preserving the viability and functional integrity of SH-SY5Y cells.

Ethical Statement

Ethical approval was not required as this study was conducted using a commercially acquired cell line.

References

  • 1. Chmielarz P, Saarma M. Neurotrophic factors for disease-modifying treatments of Parkinson’s disease: gaps between basic science and clinical studies. Pharmacol Rep. October 2020;72(5):1195-1217.
  • 2. Bhatt R, Vaishnav D, Airao V, et al. Neuroprotective potential of saroglitazar in 6-OHDA induced Parkinson’s disease in rats. Chem Biol Drug Des. July 30 2023.
  • 3. Camicioli RM, Colosimo C. Neuropsychiatric symptoms and Parkinson disease: are we looking carefully enough? Neurology. 2023.
  • 4. Ferah Okkay I, Okkay U, Cicek B, et al. Neuroprotective effect of bromelain in 6-hydroxydopamine induced in vitro model of Parkinson’s disease. Mol Biol Rep. 2021;48(12):7711-7717.
  • 5. Ashok A, Andrabi SS, Mansoor S, Kuang Y, Kwon BK, Labhasetwar V. Antioxidant therapy in oxidative stress-induced neurodegenerative diseases: role of nanoparticle-based drug delivery systems in clinical translation. Antioxidants (Basel). 2022;11(2)
  • 6. Frye CA. Neurosteroids’ effects and mechanisms for social, cognitive, emotional, and physical functions. Psych oneur oendo crino logy. 2009;34(suppl 1):S143-S161.
  • 7. Chang KH, Chen CM. The role of oxidative stress in Parkinson’s disease. Antioxidants (Basel). 2020;9(7)
  • 8. Borowicz KK, Piskorska B, Banach M, Czuczwar SJ. Neuroprotective actions of neurosteroids. Front Endocrinol (Lausanne). 2011;2:50.
  • 9. Smith CC, Gibbs TT, Farb DH. Pregnenolone sulfate as a modulator of synaptic plasticity. Psychopharmacology. 2014;231(17):3537-3556.
  • 10. Morsy MA, Abdel-Gaber SA, Mokhemer SA, et al. Pregnenolone inhibits doxorubicin-induced cardiac oxidative stress, inflammation, and apoptosis-role of matrix metalloproteinase 2 and NADPH oxidase 1. Pharmaceuticals (Basel). 2023;16(5)
  • 11. Zhi SM, Fang GX, Xie XM, et al. Melatonin reduces OGD/R-induced neuron injury by regulating redox /infl ammat ion/a popto sis signaling. Eur Rev Med Pharmacol Sci. 2020;24(3):1524-1536.
  • 12. Okkay U, Ferah Okkay I, Aydin IC, et al. Effects of Achillea millefolium on cisplatin induced ocular toxicity: an experimental study. Cutan Ocul Toxicol. 2021;40(3):214-220.
  • 13. Ferah Okkay I, Okkay U, Aydin IC, et al. Centella asiatica extract protects against cisplatin-induced hepatotoxicity via targeting oxidative stress, inflammation, and apoptosis. Environ Sci Pollut Res Int. 2022;29(22):33774-33784.
  • 14. Ferah Okkay I, Okkay U, Gundogdu OL, et al. Syringic acid protects against thioacetamide-induced hepatic encephalopathy: behavioral, biochemical, and molecular evidence. Neurosci Lett. 2022;769: 136385.
  • 15. Okkay U, Ferah Okkay I, Cicek B, Aydin IC, Ozkaraca M. Hepatoprotective and neuroprotective effect of taxifolin on hepatic encephalopathy in rats. Metab Brain Dis. 2022;37(5):1541-1556.
  • 16. Campagnolo M, Emmi A, Biundo R, et al. The pharmacological management of the behavioral aspects of Parkinson’s disease: an update. Expert Opin Pharmacother. 2023:1-9.
  • 17. Feng Mj, Zhang L, Liu Z, Zhou P, Lu X. The expression and release of Hsp60 in 6-OHDA induced in vivo and in vitro models of Parkinson’s disease. Neurochem Res. 2013;38(10):2180-2189.
  • 18. Ferlazzo N, Cirmi S, Maugeri A, et al. Neuroprotective effect of bergamot juice in 6-OHDA-induced SH-SY5Y cell death, an in vitro model of Parkinson’s disease. Pharmaceutics. 2020;12(4)
  • 19. Li Q, Li S, Fang J, et al. Artemisinin confers neuroprotection against 6-OHDA-induced neuronal injury in vitro and in vivo through activation of the ERK1/2 pathway. Molecules. 2023;28(14)
  • 20. Kovalevich J, Langford D. Considerations for the use of SH-SY5Y neuroblastoma cells in neurobiology. Methods Mol Biol. 2013;1078:9-21.
  • 21. Singh A, Kukreti R, Saso L, Kukreti S. Oxidative stress: A key modulator in neurodegenerative diseases. Molecules. 2019;24(8)

Details

Primary Language English
Subjects Pharmacology and Pharmaceutical Sciences (Other)
Journal Section Research Articles
Authors

Irmak FERAH OKKAY 0000-0001-8836-9547

Fatma YEŞİLYURT 0000-0002-1336-6322

Ufuk OKKAY 0000-0002-2871-0712

Publication Date October 9, 2023
Published in Issue Year 2023 Volume: 3 Issue: 4

Cite

EndNote FERAH OKKAY I, YEŞİLYURT F, OKKAY U (October 1, 2023) Neuroprotective Effects of Pregnenolone Against Oxidative Damage in a 6-Hydroxyd opamine-Induced Parkinson’s Disease Cell Model Using SH-SY5Y Cell Line. Pharmata 3 4 74–77.

Content of this journal is licensed under a Creative Commons Attribution NonCommercial 4.0 International License

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