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RETRACTED ARTICLE: Neuronal degeneration and oxidative stress in the SNc of 6-OHDA intoxicated rats; improving role of silymarin long-term treatment

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Abstract

Progressive loss in dopaminergic neurons (DA) of substantia nigra pars compacta (SNc) leads to Parkinson’s disease with a hypothesis of oxidative stress generation. The present study was conducted to determine the long-term efficacy of silymarin (SM) post-treatment on 6-OHDA–induced oxidative stress in the SNc of male rats. Male Wistar rats were received 6-OHDA (8 μg/rat) into SNc. After 3 weeks, as recovery period, the animals were treated with i.p. injection of SM at different doses of 100, 200, or 300 mg/kg for 15 days. At the end of the treatment, motor function, neuronal cell count, antioxidant enzymes, and lipid peroxidation and tyrosine hydroxylase (TH) activities were evaluated in the ventral midbrain tissue. The 6-OHDA significantly decreased (p ≤ 0.05) motor function, antioxidant enzyme activity, GSH level, and GSH/GSSG ratio and caused an augmentation in GSSG and lipid peroxidation level. The 6-OHDA also reduced the population of neurons and TH expression. The SM repaired the 6-OHDA–induced motor impairment, antioxidant enzyme suppression, and TH down-regulation. All three doses of SM could restore the MDA level to the normal range in the 6-OHDA–lesioned rats and could reversed the effect of 6-OHDA on GSH, GSSG level, and GSH/GSSG ratio. The SM treatment significantly and dose-dependently increased (p ≤ 0.001) the total number of surviving neurons in the SNc. Silymarin chronic treatment restored the brain’s antioxidant capacity and salvaged neurons from oxidative stress-induced neurodegeneration. The SM could also improve motor function in parkinsonian animals by increasing TH expression. These results recommend that application of SM over initial clinical stages may depict a hopeful approach versus PD. However, more research is needed to confirm this issue.

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Acknowledgments

The authors would like to thank the Research and Technology Vice-Chancellor of Hamadan University of Medical Sciences (Hamadan, Iran) for financial support of this study (grant no.: 950207475).

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, School of Pharmacy, Herbal Medicine and Natural Product Research Center,, Hamadan University of Medical Sciences, Hamadan, Iran

    Rasool Haddadi

  2. Faculty of Pharmacy, Hamadan University of Medical Sciences and Health Services, Shahid Fahmide St, Hamadan, Iran

    Rasool Haddadi

  3. Neurosurgery Research Group (NRG), Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran

    Shahla Eyvari-Brooshghalan, Mohammadmahdi Sabahi & Sara Ami Ahmadi

  4. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Alireza Mohajjel Nayebi

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  1. Rasool Haddadi
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Contributions

RH, the supervisor of the study, was involved in the concept, design, and support of the study and drafting and final checking of the manuscript. SEB carried out the statistical analyses and drafting. AMN participated and involved in the interpretation of data and final check of the draft and helped to revise the manuscript. MS involved in doing biochemical analyses and drafting. SAA involved in doing preparation of histological slides and biochemical analyses and drafting. All authors read and approved the final manuscript.

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Correspondence to Rasool Haddadi.

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This article has been retracted. Please see the retraction notice for more detail:https://doi.org/10.1007/s00210-023-02898-4

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Haddadi, R., Eyvari-Brooshghalan, S., Nayebi, A.M. et al. RETRACTED ARTICLE: Neuronal degeneration and oxidative stress in the SNc of 6-OHDA intoxicated rats; improving role of silymarin long-term treatment. Naunyn-Schmiedeberg's Arch Pharmacol 393, 2427–2437 (2020). https://doi.org/10.1007/s00210-020-01954-7

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