INHIBITORY EFFECTS OF CALCIUM-ANTAGONISTS ON MITOCHONDRIAL SWELLING-INDUCED BY LIPID-PEROXIDATION OR ARACHIDONIC-ACID IN THE RAT-BRAIN IN-VITRO

Inhibitory effects of calcium antagonists, efonidipine (NZ-105), nicardipine, nifedipine, nimodipine and flunarizine, on mitochondrial swelling induced by lipid peroxidation or arachidonic acid in the rat brain in vitro were investigated. Mitochondrial swelling and lipid peroxidation induced by FeSO4 and ascorbic acid system showed a close and significant relationship. Mitochondrial swelling and lipid peroxidation induced by FeSO4 and ascorbic acid were inhibited by all of calcium antagonists tested. The order of inhibition was: flunarizine > nicardipine > efonidipine > nimodipine > nifedipine. This result suggests that calcium antagonists tested have antiperoxidant activities resulting in protection of mitochondrial membrane damage and that each moiety of these structures would play an important role in appearance of anti-peroxidant activities. Furthermore, flunarizine and efonidipine inhibited mitochondrial swelling induced by arachidonic acid, which is not associated with lipid peroxidation. In contrast, nicardipine, nifedipine, and nimodipine did not inhibited this swelling. It is possible that flunarizine and efonidipine could directly interact with mitochondrial membrane. In conclusion, it is capable that calcium antagonists tested may protect from the membrane damage induced by lipid peroxidation and that flunarizine and efonidipine could stabilize the membrane, which is attributed to a direct interaction with the membrane.