Antioxidative and anti-inflammatory effects of four cysteine-containing agents in striatum of MPTP-treated mice

Objectives: Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were used to examine the neuroprotective effects of n-acetyl cysteine (NAC), s-ethyl cysteine (SEC), s-methyl cysteine (SMC), and s-propyl cysteine (SPC). Methods: Each agent at 1 g/L was directly added to the drinking water for 3 wk. 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 the striatum was collected for analyses. Results: The MPTP treatment significantly depleted striatal 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-alpha (TNF-alpha) levels in striatum (P < 0.05). 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-alpha (P. < 0.05). MPTP treatment significantly suppressed GPX mRNA expression and enhanced TNF-a mRNA expression (P < 0.05). Compared with MPTP treatment alone, the pre-intake of NAC, SEC, SMC, and SPC significantly elevated GPX mRNA expression and diminished TNF-a mRNA expression (P < 0.05), in which SPC showed the greatest suppressive effect against MPTP-induced TNF-a mRNA expression (P < 0.05). Dopamine and 3,4-dihydroxyphenylacetic acid contents in the striatum were significantly decreased by MPTP treatment (P < 0.05). The pye-intake of four test agents significantly improved MPTP-induced dopamine depletion and increased dopamine/3,4-dihydroxyphenylacetic acid content (P < 0.05). Conclusion: These results suggest that these cysteine-containing compounds could provide anti-oxidative and anti-inflammatory protection for the striatum against the development of Parkinson's disease. (c) 2007 Elsevier Inc. All rights reserved..