Neuroprotection by lomerizine, a prophylactic drug for migraine, against hydrogen peroxide-induced hippocampal neurotoxicity.

Publisher: Springer Country of Publication: Netherlands NLM ID: 0364456 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-4919 (Electronic) Linking ISSN: 03008177 NLM ISO Abbreviation: Mol Cell Biochem Subsets: MEDLINE

Publication: New York : Springer
Original Publication: The Hague, Dr. W. Junk B. V. Publishers.

Hippocampus/*pathology ; Hydrogen Peroxide/*toxicity ; Migraine Disorders/*drug therapy ; Migraine Disorders/*prevention & control ; Neuroprotective Agents/*therapeutic use ; Neurotoxicity Syndromes/*drug therapy ; Piperazines/*therapeutic use; Animals ; Benzamides/pharmacology ; Calcium/metabolism ; Calcium Channel Blockers/pharmacology ; Cell Death/drug effects ; Cells, Cultured ; HEK293 Cells ; Hippocampus/drug effects ; Humans ; Intracellular Space/drug effects ; Intracellular Space/metabolism ; Ion Channel Gating/drug effects ; Migraine Disorders/pathology ; Neurons/drug effects ; Neurons/metabolism ; Neurons/pathology ; Neuroprotective Agents/pharmacology ; Neurotoxicity Syndromes/pathology ; Nifedipine/pharmacology ; Piperazines/pharmacology ; Potassium Chloride/pharmacology ; Rats ; Rats, Wistar ; TRPC Cation Channels/metabolism ; TRPM Cation Channels/metabolism

Migraine is one of the risk factor for ischemic stroke. The purpose of this study was to examine the effect of lomerizine, a prophylactic drug for migraine, on H(2)O(2)-induced cell death of hippocampal neurons. Cytosolic Ca(2+) concentration was measured using fura-2 as a Ca(2+) indicator. Cell death was estimated by trypan blue exclusion. In rat-cultured hippocampal neurons, the addition of H(2)O(2) induced biphasic Ca(2+) elevations and cell death. The H(2)O(2)-induced biphasic Ca(2+) elevations and cell death only occurred when extracellular Ca(2+) was present. The biphasic Ca(2+) elevation was mediated by Ca(2+) influx through the plasma membrane, but not Ca(2+) release from the intracellular Ca(2+) store. Both the early and late phases of H(2)O(2)-induced Ca(2+) influx were reduced by either a T- or L-type voltage-dependent Ca(2+) channel (VDCC) blocker, lomerizine. In fact, L-type VDCC (α(1C) subunit) and T-type VDCC (α(1G) subunit) mRNA were expressed in rat hippocampal neurons. Although an L-type VDCC blocker, nifedipine, partly suppressed the late phase of Ca(2+) influx in response to H(2)O(2), a T-type VDCC blocker, mibefradil, reduced both phases of Ca(2+) influx. Moreover, lomerizine and mibefradil strongly reduced H(2)O(2)-induced cell death, and nifedipine weakly reduced it. These findings suggest that the inhibition of H(2)O(2)-induced Ca(2+) influx through T-type VDCC seems to be important in the protective effect of lomerizine against oxidative stress. It is possible that lomerizine may be a useful drug for prophylactic treatment of migraine, because migraine is a risk factor for ischemic stroke.

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0 (Benzamides)
0 (Calcium Channel Blockers)
0 (Neuroprotective Agents)
0 (Piperazines)
0 (TRPC Cation Channels)
0 (TRPM Cation Channels)
0 (Trpc5 protein, rat)
0 (Trpm2 protein, rat)
660YQ98I10 (Potassium Chloride)
8J365YF1YH (3-aminobenzamide)
BBX060AN9V (Hydrogen Peroxide)
DEE37CY4VO (lomerizine)
I9ZF7L6G2L (Nifedipine)
SY7Q814VUP (Calcium)

Date Created: 20110610 Date Completed: 20120221 Latest Revision: 20211020

20240829

10.1007/s11010-011-0913-3

21656126