Federal University of Pampa - Campus Uruguaiana, Uruguaiana, CEP 97500-970, RS, Brazil.
Regional University of the Northwest of the State of Rio Grande do Sul - Campus Ijuí, Ijuí, CEP 98700-000, RS, Brazil.
Metab Brain Dis. 2023 Dec;38(8):2615-2625. doi: 10.1007/s11011-023-01318-z. Epub 2023 Nov 3.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been widely used due to its specific and reproducible neurotoxic effect on the nigrostriatal system, being considered a convenient model of dopaminergic neurodegeneration to study interventions therapeutics. The purple pitanga (Eugenia uniflora) is a polyphenol-rich fruit with antioxidant and antidepressant properties, among others. Therefore, this study investigated the effect of purple pitanga extract (PPE) on acute early oxidative stress induced by intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in rats. Male Wistar rats were pre-treated orally with PPE (1000 mg/kg) or vehicle. After 24 h, MPTP (0.1 mg/10µL/nostril) or vehicle was administered bilaterally into the animal's nostrils, and 6 h later, the olfactory bulb (OB), striatum (ST), and substantia nigra (SN) were collected to evaluate the oxidative stress parameters. Our findings revealed that OB and SN were the most affected areas after 6 h of MPTP infusion; an early increase in reactive oxygen species (ROS) levels was observed, while pretreatment with a single dose of PPE prevented this increment. No differences in thiobarbituric acid reactive species (TBARS) and 3-nitrotyrosine (3-NT) formation were observed, although 4-hydroxy-2-nonenal (4-HNE) levels increased, which is the most toxic form of lipid peroxidation, in the MPTP group. The PPE pretreatment could prevent this increase by increasing the NPSH levels previously decreased by MPTP. Furthermore, PPE prevents the Na+/K + ATPase strongly inhibited by MPTP, showing the neuroprotective capacity of the PPE by inhibiting the MPTP-generated oxidation. Thus, we demonstrated for the first time the antioxidant and neuroprotective effects of PPE against the early MPTP neurotoxicity.
1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)因其对黑质纹状体系统具有特异性和可重现性的神经毒性作用而被广泛应用,被认为是研究干预治疗多巴胺能神经退行性变的一种方便的模型。紫pitanga(Eugenia uniflora)是一种富含多酚的水果,具有抗氧化和抗抑郁等特性。因此,本研究旨在探讨紫pitanga 提取物(PPE)对鼻内 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)给药引起的急性早期氧化应激的影响。雄性 Wistar 大鼠经口预先用 PPE(1000mg/kg)或载体处理。24 小时后,将 MPTP(0.1mg/10µL/鼻孔)或载体双侧鼻内给药,6 小时后采集嗅球(OB)、纹状体(ST)和黑质(SN),以评估氧化应激参数。我们的研究结果表明,MPTP 输注 6 小时后,OB 和 SN 是受影响最严重的区域;观察到活性氧(ROS)水平的早期增加,而单次 PPE 预处理可防止这种增加。虽然脂质过氧化的最有毒形式 4-羟基-2-壬烯醛(4-HNE)水平增加,但未观察到丙二醛(TBARS)和 3-硝基酪氨酸(3-NT)形成的差异。MPTP 预处理可通过增加先前被 MPTP 降低的 NPSH 水平来预防这种增加。此外,PPE 可防止 MPTP 强烈抑制的 Na+/K+ATPase,通过抑制 MPTP 产生的氧化来显示 PPE 的神经保护能力。因此,我们首次证明了 PPE 对早期 MPTP 神经毒性的抗氧化和神经保护作用。