四種半胱胺酸衍生物在MPTP處理之小鼠大腦中的抗氧化與抗發炎作用

將四種親水性之半胱胺酸衍生物–N-acetyl cysteine (NAC)、S-ethyl cysteine (SEC)、S-methyl cysteine (SMC)與S-propyl cysteine (SPC)分別添加至C57BL/ 6Jnarl小鼠飲水中，3週後再以皮下注射1-methyl-4-phenyl-1,2,3,6-tetrahydro- pyridine (MPTP)連續6天，誘發大腦神經毒性傷害，產生類帕金森氏症 (Parkinson’s disease)之症狀，並檢測此四種衍生物在大腦的黑質與紋狀體中是否具有神經保護作用。 實驗結果發現，在MPTP處理的小鼠大腦中，麩胱苷肽 (GSH)的含量以及麩胱苷肽過氧化酶 (GPX)與超氧化物歧化酶 (SOD)之活性皆明顯降低 (p＜0.05)，另外，脂質過氧化產物–丙二醛 (MDA)，以及介白素-6 (IL-6)與腫瘤壞死因子 (TNF-α)的濃度皆顯著上升 (p＜0.05)。而在飲水中添加NAC、SEC、SMC與SPC的小鼠，則可減緩MPTP在大腦中誘發所引起的GSH流失、維持GPX與SOD的酵素活性、降低MDA的生成，並抑制IL-6與TNF-α濃度的上升 (p＜0.05)。 另外，MPTP處理後明顯降低小鼠大腦中多巴胺與 (Dopamine)與二羥基苯乙酸 (DOPAC)的濃度 (p＜0.05)，而在飲水中添加NAC、SEC、SMC與SPC，則可顯著改善MPTP誘發所引起的多巴胺與二羥基苯乙酸濃度之下降 (p＜0.05)。 本研究結果顯示，NAC、SEC、SMC與SPC等四種半胱胺酸之衍生物，在大腦中可以提供抗氧化與抗發炎之作用，因此具有神經保護的功能，對於帕金森氏症之形成或許具有預防或是減緩的能力。

Objectives: Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydro- pyridine (MPTP) were used to examine the neuroprotective effects of N-acetyl cysteine (NAC), S-ethyl cysteine (SEC), S-methyl cysteine (SMC), S-propyl cysteine (SPC).Methods: Each agent at 1 g/L was directly added to the drinking water for 3 weeks. Mice were treated by subcutaneous injection of MPTP (24 mg/kg body weight) for 6 consecutive days. The brain from each mouse was quickly removed and collected for analyses.Results: The MPTP treatment significantly depleted brain’s glutathione content, reduced the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase, increased malondialdehyde level, and elevated interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels in the brain (p＜0.05). However, the pre- intake of NAC, SEC, SMC, and SPC significantly attenuated MPTP-induced glutathione loss, retained the activity of GPX and SOD, diminished oxidative stress, and suppressed MPTP-induced elevation of IL-6 and TNF-α (p＜0.05). We also confirmed that dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) contents in the brain were significantly decreased by MPTP treatment (p＜0.05). Importantly, the pre-intake of four cysteine-containing compounds significantly improved MPTP- induced dopamine depletion and increased dopamine/DOPAC content (p＜0.05).Conclusion: These results suggest that these cysteine-containing compounds could provide antioxidative and anti-inflammatory protection for the brain against the development of Parkinson’s disease.