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), nicar dipine, nifedipine, nimodipine and flunarizine, on mitochondrial swell ing induced by lipid peroxidation or arachidonic acid in the rat brain in vitro were investigated. Mitochondrial swelling and lipid peroxida tion induced by FeSO4 and ascorbic acid system showed a close and sign ificant relationship. Mitochondrial swelling and lipid peroxidation in duced by FeSO4 and ascorbic acid were inhibited by all of calcium anta gonists tested. The order of inhibition was: flunarizine > nicardipine > efonidipine > nimodipine > nifedipine. This result suggests that ca lcium antagonists tested have antiperoxidant activities resulting in p rotection of mitochondrial membrane damage and that each moiety of the se structures would play an important role in appearance of anti-perox idant activities. Furthermore, flunarizine and efonidipine inhibited m itochondrial swelling induced by arachidonic acid, which is not associ ated with lipid peroxidation. In contrast, nicardipine, nifedipine, an d nimodipine did not inhibited this swelling. It is possible that flun arizine and efonidipine could directly interact with mitochondrial mem brane. In conclusion, it is capable that calcium antagonists tested ma y protect from the membrane damage induced by lipid peroxidation and t hat flunarizine and efonidipine could stabilize the membrane, which is attributed to a direct interaction with the membrane.