Excitotoxicity in rat's brain induced by exposure of manganese and neuroprotective effects of pinacidil and nimodipine.
Manganese (Mn) is an essential trace element for humans. However, manganism would be caused by excessive Mn. The mechanisms underlying excitotoxicity induced by manganism are poorly understood. As it is known to us, glutamate (Glu) is the most prevalent excitatory neurotransmitter. To determine the possible role of dysfunction of Glu transportation and metabolism in Mn-induced excitotoxicity, the rats were ip injected with different dose of MnCl(2) (0, 50, 100, and 200 micromol/kg), the levels of Mn and activities of GS, PAG, Na(+)-K(+)-ATPase, and Ca(2+)-ATPase in striatum were investigated. In addition, effect of 20.38 micromol/kg pinacidil (K(+) channel opener) or 2.4 micromol/kg nimodipine (Ca(2+) channel blocker) were studied at 200 micromol/kg MnCl(2). With dose-dependent inhibition of GS, Na(+)-K(+)-ATPase, and Ca(2+)-ATPase activities, increase of Mn levels and PAG activity were observed. Further investigation indicated that pre-treatment of pinacidil or nimodipine reversed toxic effect of MnCl(2) significantly. These results suggested that MnCl(2) could induce dysfunction of Glu transportation and metabolism by augmenting the excitotoxicity dose-dependently; pinacidil and nimodipine might antagonize manganese neurotoxicity.
Deng
Yu
Y
Department of environmental health, School of Public Health, China Medical University, Shenyang, People's Republic of China.
Xu
Zhaofa
Z
Xu
Bin
B
Tian
Yawen
Y
Deng
Xiaoqiang
X
Xin
Xin
X
Gao
Jian
J
D000818:Animals; D002712:Chlorides / Q000633:toxicity; D003342:Corpus Striatum / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D017895:Manganese Compounds; D020149:Manganese Poisoning; D049990:Membrane Transport Modulators / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology*; D020110:Pinacidil / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D002712:Chlorides; D017895:Manganese Compounds; D049990:Membrane Transport Modulators; D018696:Neuroprotective Agents; D009553:Nimodipine; D020110:Pinacidil; C025340:manganese chloride