[Effect of N-acetyl-cysteine and depakine pretreatment on ferrous chloride-induced membrane potential and peroxidate changes in rat cortex neurons].
OBJECTIVE
To investigate the effect of N-acetyl-cysteine (NAC) and depakine (DP) on the changes of membrane potential and peroxidate in rat cortex neurons exposed to ferrous chloride (FeCl(2)).


METHODS
Cultured cortex neurons of newly born SD rats were randomly divided into control group (PBS group), model group (FeCl(2) group), NAC pretreatment group (NAC group), DP pretreatment group (DP group) and NAC+DP pretreatment group (NAC+DP group). In the latter three groups, NAC (0.08 mg/ml) and DP (0.1 mg/ml) were added in the cell culture 2 and 3 h before FeCl(2) (1 mmol/L) exposure, respectively. After exposure to FeCl(2), the membrane potential of the neurons was detected with fluorescent dye DiBAC4(3) (bis-(1,3-dibutylbarbituric acid) trimethine oxonol), and the peroxidate level with 2,7-dichlorofluorescin diacetate (H(2)DCF) by laser confocal scanning microscope (LCSM) and nuclear factor-KappaB (NF-KappaB) level with immunocytochemistry.


RESULTS
Compared with FeCl(2) group, the expression of NF-KappaB and peroxidate level in the neurons were decreased significantly in NAC and NAC+DP groups (P<0.01), but not in DP group (P>0.05). FeCl(2) depolarized the membrane potential and increased the expression of NF-KappaB in the neurons. Compared with FeCl(2) group, significant changes in the membrane potential were observed in DP and NAC+DP groups (P<0.01) but not in NAC or PBS group (P>0.05).


CONCLUSIONS
Both NAC and DP can protect the neurons from FeCl(2)-induced damage but through different pathways, and their combined use can significantly alleviate neuronal damages due to FeCl(2) exposure. Antioxidants such as NAC in combination with antiepileptic drugs may produce favorable effect in prevention and treatment of posttraumatic epilepsy.
Lin
Yuan-xiang
YX
Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China. lyx99070@163.com
Xu
Ru-xiang
RX
Jiang
Xiao-dan
XD
Kang
De-zhi
DZ
Ke
Yi-quan
YQ
Du
Mou-xuan
MX
Cai
Ying-qian
YQ
Qin
Ling-sha
LS
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005296:Ferrous Compounds / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D010545:Peroxides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014635:Valproic Acid / Q000494:pharmacology*
D005296:Ferrous Compounds; D018696:Neuroprotective Agents; D010545:Peroxides; D014635:Valproic Acid; C029451:ferrous chloride; D000111:Acetylcysteine