Catalytic metalloporphyrin protects against paraquat neurotoxicity in vivo.
OBJECTIVE
To examine the neuroprotective effects of a novel manganese porphyrin, manganese (III) meso-tetrakis (N,N'-diethylimidazolium-2-yl) porphyrin (MnTDM), in the mouse model of Parkinson's disease (PD) induced by paraquat (PQ).


METHODS
Male C57BL/6 mice were subcutaneously injected with either saline or PQ at 2-day intervals for a total of 10 doses, MnTDM was subcutaneously injected with the PQ 2 h before treatment. Performance on the pole and swim test were measured 7 days after the last injection and animals were sacrificed one day later. Levels of dopamine (DA) and its metabolites in the striatum were measured by high-performance liquid chromatography with an electrochemical detector (HPLC-ECD). Thiobarbituric acid (TBA) method was used to assay the lipid peroxidation product, malondialdehyde (MDA), and the number of tyrosine hydroxylase (TH) positive neurons was estimated using immunohistochemistry.


RESULTS
Pretreatment with MnTDM significantly attenuated PQ-impaired behavioral performance, depleted dopamine content in striata, increased MDA, and dopaminergic neuron loss in the substantia nigra.


CONCLUSIONS
Oxidative stress plays an important role in PQ-induced neurotoxicity which can be potentially prevented by manganese porphyrin. These findings also propose a possible therapeutical strategy for neurodegenerative disorders associated with oxidative stress such as PD.
Chen
Ping
P
School of Life Science and Technology, Tongji University, Shanghai 200092, China.
Chen
Zhen
Z
Li
Ang
A
Lou
Xiao-Chu
XC
Wu
Xiao-Kang
XK
Zhao
Chun-Jun
CJ
Wang
Shi-Long
SL
Liang
Li-Ping
LP
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D002384:Catalysis; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008665:Metalloporphyrins / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010269:Paraquat; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
C472668:AEOL 10150; D000975:Antioxidants; D000978:Antiparkinson Agents; D008665:Metalloporphyrins; D018696:Neuroprotective Agents; D008315:Malondialdehyde; D014446:Tyrosine 3-Monooxygenase; D010269:Paraquat; D004298:Dopamine