The homeostasis of iron and suppression of HO-1 involved in the protective effects of nimodipine on neurodegeneration induced by aluminum overloading in mice.
Aluminum intoxication can cause damage to the cognitive function and neurodegenerative diseases. In the present study, we investigated the role of iron homeostasis and heme oxygenase-1 (HO-1) expression in the protective effects of nimodipine on the neurodegeneration induced by aluminum overloading in mice. 2 microl of 0.25% aluminum chloride solution was intracerebroventricularly injected once a day for five days to induce the neurodegeneration of mice. Nimodipine was administered by intragastric gavage (80 mg/kg per day) for 30 days. We observed that nimodipine could improve the performance of behavior test related to the learning and memory function and ameliorate pathological changes of hippocampi caused by aluminum. Results of western blot, immunohistochemistry study, biochemical test and inductively coupled plasma-atomic emission spectrometry showed that nimodipine could suppress the increased expression of HO-1 protein, and decrease the elevation of both HO activity and iron level in hippocampi, induced by aluminum overloading. These results indicate that nimodipine can suppress the neurodegenerative development induced by aluminum overloading and the mechanism of its action is at least partly related to keeping the homeostasis of iron through blunting the expression of HO-1 in hippocampus.
Yuan
Ye
Y
Department of Pharmacology of Chong Qing Medical University, China.
Guo
Jian-Zeng
JZ
Zhou
Qi-Xin
QX
D000535:Aluminum / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006706:Homeostasis / Q000187:drug effects*; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D007501:Iron / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D018696:Neuroprotective Agents; D009553:Nimodipine / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D013028:Space Perception / Q000187:drug effects; D013054:Spectrophotometry, Atomic
D002121:Calcium Channel Blockers; D007202:Indicators and Reagents; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009553:Nimodipine; D000535:Aluminum; D007501:Iron; D051547:Heme Oxygenase-1