Free fatty acids, lipid peroxidation, and lysosomal enzymes in experimental focal cerebral ischemia in primates: loss of lysosomal latency by lipid peroxidation.
Experimental focal cerebral ischemia was produced in monkeys (Macaca radiata) by occlusion of the right middle cerebral artery (MCA). The release of the lysosomal glycosidases, beta-D-hexosaminidase, alpha-L-fucosidase and alpha-D-mannosidase into the soluble fraction in the right basal ganglia of the experimental animals was measured at different periods from 30 min to 12 hr after occlusion and compared with the corresponding sham operated control animals. There was a significant increase in the released lysosomal enzymes in the MCA occluded animals at all periods and particularly at 4 hr after occlusion. The CSF from the experimental animals also showed elevated levels of hexosaminidase and fucosidase. The free fatty acids (FFA) measured in the basal ganglia at 30 min and 2 hr after occlusion showed a 100 fold increase in the experimental animals. The predominant fatty acid released was linoleic acid (18:2) followed by arachidonic acid (20:4). Lipid peroxidation in the basal ganglia measured by the thiobarbituric acid (TBA) reaction in the presence or absence of ascorbic acid also showed a significant increase in the experimental animals at all periods with a maximum at 30 min to 2 hr after occlusion. In order to assess whether lipid peroxidation causes damage to the lysosomes and release of the enzymes, a lysosome enriched P2 fraction from the normal monkey basal ganglia was prepared and the effect of peroxidation studied. Maximum peroxidation in the P2 fraction was observed in the presence of arachidonic acid, ascorbic acid and Fe2+.(ABSTRACT TRUNCATED AT 250 WORDS)
Nagarajan
S
S
Department of Neurological Sciences, Christian Medical College & Hospital, Vellore, India.
Theodore
D R
DR
Abraham
J
J
Balasubramanian
A S
AS
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001479:Basal Ganglia / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005260:Female; D006867:Hydrolases / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism*; D008247:Lysosomes / Q000201:enzymology*; D008251:Macaca / Q000378:metabolism*; D008255:Macaca radiata / Q000378:metabolism*; D008297:Male; D008361:Mannosidases / Q000378:metabolism; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D005644:alpha-L-Fucosidase / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D000975:Antioxidants; D005231:Fatty Acids, Unsaturated; D008054:Lipid Peroxides; D006867:Hydrolases; D008361:Mannosidases; D005644:alpha-L-Fucosidase; D001619:beta-N-Acetylhexosaminidases