Vitamin E Analog Trolox Attenuates MPTP-Induced Parkinson’s Disease in Mice, Mitigating Oxidative Stress, Neuroinflammation, and Motor Impairment

Abstract

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.

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“…In this study, Matsura, (2019) observed that tocotrienol exerts its cytoprotection through a novel mechanism which includes membrane ERβ/PI3K/Akt signaling via caveola formation as well as its antioxidant activity. An analogue of vitamin E, Trolox was recently reported by Atiq et al (2023) to inhibit activated astrocytes (GFAP) and microglia (Iba-1), also reduces phosphorylated nuclear factor-κB, (p-NF-κB) and tumor necrosis factor-alpha (TNF-α) in the PD mouse brain. Just recently, vitamin E administration was reported to offer neuroprotective function on manganese-induced neurodegeneration in the nigrostriatal system.…”

Saponin components in Polygala tenuifolia as potential candidate drugs for treating dementia

“…Aβ 25-35 plays a significant catalytic role in this process ( Smith and Klimov, 2019 ). In patients with AD and PDD, there is often an increase in lipid hydroperoxide (L-OOH) and malondialdehyde (MDA) activity, alongside decreased activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) ( Chen et al, 2022 ; Atiq et al, 2023 ). Moreover, the brain’s rich content of metal ions, such as iron, facilitates oxidative stress and DNA damage through the Haber-Weiss reaction ( Suma et al, 2020 ), and promotes the aggregation of α-synuclein, leading to the formation of Lewy bodies—a key pathological feature of PDD and Lewy body dementia ( Wakabayashi et al, 2007 ).…”

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“…Vitamin E (α-tocopherol) is a lipid-soluble vitamin, enhancing immunity and reducing OS (Wang et al, 2023). Atiq A et al published an article regarding the impact of vitamin E using an experimental model of Parkinson's disease, reducing α-synuclein expression, increasing the expression of dopamine transporter in the substantia nigra and activating the nuclear factor erythroid-2-related factor 2 (Nrf2) pathways (Atiq et al, 2023).…”