Vitamin E Analog Trolox Attenuates MPTP-Induced Parkinson’s Disease in Mice, Mitigating Oxidative Stress, Neuroinflammation, and Motor Impairment
Trolox is a potent antioxidant and a water-soluble analog of vitamin E. It has been used in scientific studies to examine oxidative stress and its impact on biological systems. Trolox has been shown to have a neuroprotective effect against ischemia and IL-1β-mediated neurodegeneration. In this study...
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/12/9942 |
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| author | Abubakar Atiq Hyeon Jin Lee Amjad Khan Min Hwa Kang Inayat Ur Rehman Riaz Ahmad Muhammad Tahir Jawad Ali Kyonghwan Choe Jun Sung Park Myeong Ok Kim |
| author_facet | Abubakar Atiq Hyeon Jin Lee Amjad Khan Min Hwa Kang Inayat Ur Rehman Riaz Ahmad Muhammad Tahir Jawad Ali Kyonghwan Choe Jun Sung Park Myeong Ok Kim |
| author_sort | Abubakar Atiq |
| collection | DOAJ |
| description | Trolox is a potent antioxidant and a water-soluble analog of vitamin E. It has been used in scientific studies to examine oxidative stress and its impact on biological systems. Trolox has been shown to have a neuroprotective effect against ischemia and IL-1β-mediated neurodegeneration. In this study, we investigated the potential protective mechanisms of Trolox against a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease mouse model. Western blotting, immunofluorescence staining, and ROS/LPO assays were performed to investigate the role of trolox against neuroinflammation, the oxidative stress mediated by MPTP in the Parkinson’s disease (PD) mouse model (wild-type mice (C57BL/6N), eight weeks old, average body weight 25–30 g). Our study showed that MPTP increased the expression of α-synuclein, decreased tyrosine hydroxylase (TH) and dopamine transporter (DAT) levels in the striatum and substantia nigra pars compacta (SNpc), and impaired motor function. However, Trolox treatment significantly reversed these PD-like pathologies. Furthermore, Trolox treatment reduced oxidative stress by increasing the expression of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Lastly, Trolox treatment inhibited the activated astrocytes (GFAP) and microglia (Iba-1), also reducing phosphorylated nuclear factor-κB, (p-NF-κB) and tumor necrosis factor-alpha (TNF-α) in the PD mouse brain. Overall, our study demonstrated that Trolox may exert neuroprotection on dopaminergic neurons against MPTP-induced oxidative stress, neuroinflammation, motor dysfunction, and neurodegeneration. |
| first_indexed | 2024-03-11T02:22:36Z |
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| language | English |
| last_indexed | 2024-03-11T02:22:36Z |
| publishDate | 2023-06-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-822f90469b574e98a45d9af810b8b0372023-11-18T10:46:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-012412994210.3390/ijms24129942Vitamin E Analog Trolox Attenuates MPTP-Induced Parkinson’s Disease in Mice, Mitigating Oxidative Stress, Neuroinflammation, and Motor ImpairmentAbubakar Atiq0Hyeon Jin Lee1Amjad Khan2Min Hwa Kang3Inayat Ur Rehman4Riaz Ahmad5Muhammad Tahir6Jawad Ali7Kyonghwan Choe8Jun Sung Park9Myeong Ok Kim10Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of KoreaDivision of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of KoreaDivision of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of KoreaDivision of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of KoreaDivision of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of KoreaDivision of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of KoreaDivision of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of KoreaDivision of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of KoreaDivision of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of KoreaDivision of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of KoreaDivision of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of KoreaTrolox is a potent antioxidant and a water-soluble analog of vitamin E. It has been used in scientific studies to examine oxidative stress and its impact on biological systems. Trolox has been shown to have a neuroprotective effect against ischemia and IL-1β-mediated neurodegeneration. In this study, we investigated the potential protective mechanisms of Trolox against a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease mouse model. Western blotting, immunofluorescence staining, and ROS/LPO assays were performed to investigate the role of trolox against neuroinflammation, the oxidative stress mediated by MPTP in the Parkinson’s disease (PD) mouse model (wild-type mice (C57BL/6N), eight weeks old, average body weight 25–30 g). Our study showed that MPTP increased the expression of α-synuclein, decreased tyrosine hydroxylase (TH) and dopamine transporter (DAT) levels in the striatum and substantia nigra pars compacta (SNpc), and impaired motor function. However, Trolox treatment significantly reversed these PD-like pathologies. Furthermore, Trolox treatment reduced oxidative stress by increasing the expression of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Lastly, Trolox treatment inhibited the activated astrocytes (GFAP) and microglia (Iba-1), also reducing phosphorylated nuclear factor-κB, (p-NF-κB) and tumor necrosis factor-alpha (TNF-α) in the PD mouse brain. Overall, our study demonstrated that Trolox may exert neuroprotection on dopaminergic neurons against MPTP-induced oxidative stress, neuroinflammation, motor dysfunction, and neurodegeneration.https://www.mdpi.com/1422-0067/24/12/9942trolox1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)neurodegenerationneuroinflammationoxidative stresssubstantia nigra pars compacta (SNpc) |
| spellingShingle | Abubakar Atiq Hyeon Jin Lee Amjad Khan Min Hwa Kang Inayat Ur Rehman Riaz Ahmad Muhammad Tahir Jawad Ali Kyonghwan Choe Jun Sung Park Myeong Ok Kim Vitamin E Analog Trolox Attenuates MPTP-Induced Parkinson’s Disease in Mice, Mitigating Oxidative Stress, Neuroinflammation, and Motor Impairment International Journal of Molecular Sciences trolox 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurodegeneration neuroinflammation oxidative stress substantia nigra pars compacta (SNpc) |
| title | Vitamin E Analog Trolox Attenuates MPTP-Induced Parkinson’s Disease in Mice, Mitigating Oxidative Stress, Neuroinflammation, and Motor Impairment |
| title_full | Vitamin E Analog Trolox Attenuates MPTP-Induced Parkinson’s Disease in Mice, Mitigating Oxidative Stress, Neuroinflammation, and Motor Impairment |
| title_fullStr | Vitamin E Analog Trolox Attenuates MPTP-Induced Parkinson’s Disease in Mice, Mitigating Oxidative Stress, Neuroinflammation, and Motor Impairment |
| title_full_unstemmed | Vitamin E Analog Trolox Attenuates MPTP-Induced Parkinson’s Disease in Mice, Mitigating Oxidative Stress, Neuroinflammation, and Motor Impairment |
| title_short | Vitamin E Analog Trolox Attenuates MPTP-Induced Parkinson’s Disease in Mice, Mitigating Oxidative Stress, Neuroinflammation, and Motor Impairment |
| title_sort | vitamin e analog trolox attenuates mptp induced parkinson s disease in mice mitigating oxidative stress neuroinflammation and motor impairment |
| topic | trolox 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurodegeneration neuroinflammation oxidative stress substantia nigra pars compacta (SNpc) |
| url | https://www.mdpi.com/1422-0067/24/12/9942 |
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