TRILINOLEIN PRESERVES MITOCHONDRIA ULTRASTRUCTURE IN ISOLATED RAT-HEART SUBJECTED TO GLOBAL-ISCHEMIA THROUGH ANTIOXIDANT ACTIVITY AS MEASURED BY CHEMILUMINESCENCE
P. Chan et al., TRILINOLEIN PRESERVES MITOCHONDRIA ULTRASTRUCTURE IN ISOLATED RAT-HEART SUBJECTED TO GLOBAL-ISCHEMIA THROUGH ANTIOXIDANT ACTIVITY AS MEASURED BY CHEMILUMINESCENCE, Pharmacology, 52(4), 1996, pp. 216-225
Oxygen-derived free radicals (OFR) have been proposed as the cause of
myocardial damage through lipid peroxidation during ischemia and reper
fusion. Antioxidants can effectively ameliorate the damage induced by
lipid peroxidation. Trilinolein is a triacylglycerol recently purified
from the well known traditional Chinese herb Panax pseudoginseng, whi
ch has been used in treating circulatory disorders among Chinese for h
undreds of years; it has linoleate as the only fatty acid residue in a
ll three esterified positions of glycerol. This chemical has recently
been demonstrated to have antioxidant activity by enhanced chemilumine
scence. The addition of phorbol myristic acetate (PMA) to medium conta
ining leukocytes produces OFR; this phenomenon was measured by chemilu
minescence. Addition of trilinolein to medium containing leukocytes pr
eceding the addition of PMA suppressed the production of OFR. The cont
rol value of chemiluminescence of a medium containing leukocytes with
addition of PMA was 9.23 +/- 1.19 x 10(3) mV. The most effective conce
ntration of trilinolein was 10(-7) mol/l which decreased the signals t
o 4.59 +/- 0.02 x 10(3) mV (p < 0.001). The antioxidant effect had a c
oncentration-response curve similar to alpha-tocopherol. After pretrea
tment for 15 min with trilinolein at a concentration of 10(-7) mol/l i
n isolated perfused rat heart which had been subjected to 60 min of gl
obal ischemia, the integrity of the rat heart mitochondria was preserv
ed as examined under the electron microscope. No swelling of mitochond
ria occurred and there was good alignment of cristae and absence of am
orphous density. Previous experiments have shown that trilinolein can
also improve erythrocyte deformability in vitro. Infarct size reductio
n of about 50% was also demonstrated in in vivo rat heart subjected to
4 h coronary occlusion, The mechanism of myocardial protection, in ad
dition to the antioxidant effect, is suggested as maintaining the memb
rane fluidity of cardiomyocytes.