Antioxidative and anti-inflammatory effects of four cysteine-containing agents in striatum of MPTP-treated mice.
OBJECTIVE
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-alpha 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-alpha mRNA expression (P < 0.05), in which SPC showed the greatest suppressive effect against MPTP-induced TNF-alpha 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 pre-intake of four test agents significantly improved MPTP-induced dopamine depletion and increased dopamine/3,4-dihydroxyphenylacetic acid content (P < 0.05).


CONCLUSIONS
These results suggest that these cysteine-containing compounds could provide antioxidative and anti-inflammatory protection for the striatum against the development of Parkinson's disease.
Chen
Chiu-mei
CM
Department of Neurology, Chung Shan Medical University Hospital, Taichung City, Taiwan.
Yin
Mei-chin
MC
Hsu
Cheng-chin
CC
Liu
Ting-chun
TC
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D002374:Catalase / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology*; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D020267:MPTP Poisoning; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity; D010300:Parkinson Disease / Q000517:prevention & control; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D018696:Neuroprotective Agents; D009498:Neurotoxins; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; C028742:S-propylcysteine; C008425:S-methylcysteine; C026826:S-ethylcysteine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D003545:Cysteine; D000111:Acetylcysteine