Lipid alterations induced by renal ischemia: pathogenic factor in membrane damage.
Lipids of the renal cortex and outer stripe of outer medulla were analyzed in rats during ischemia and 2 hr after blood reflow. After 15 min of ischemia, there were marked elevations of free fatty acids (FFA) and diacylglycerol (DG), increasing further at 60 min. Percentile increases were greater for polyunsaturated FFA. These elevations were accompanied by alterations in phospholipids (PL): Elevations of lysophosphatidylcholine (LPC) at 15 min, phosphatidic acid at 15 and 60 min, and declines of phosphatidylcholine and phosphatidylinositol at 60 min. Triacylglycerol (TG) showed only modest decline, at 60 min, and in insufficient degree to account for increments in FFA and DG. Two hours after 15 min of ischemia, LPC returned to control levels and other PL were normal except phosphatidylinositol which was decreased, and phosphatidic acid, which remained elevated. FFA and DG approached or reached control values. Two hours after 60 min of ischemia, LPC, FFA, DGs and phosphatidic acid remained elevated; phosphatidylcholine and phosphatidylinositol remained decreased. Histological injury was seen 2 and 24 hr after blood reflow only in kidneys injured by 60 min of ischemia. Thus, irreversible ischemic damage correlates with persistent abnormalities of phosphatidylcholine metabolism and persistent elevations of FFA, LPC, and DG. It is not known whether lipids break down at normal or accelerated rates during ischemia. In this context, accumulation of lipid breakdown products in ischemic cells may be due to failure of their reutilization, or disposal. Similarly, depletion of phospholipids during ischemia may be due to the inability of cells to reconstitute the lipid following degradation.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000473:pathology; D004075:Diglycerides / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism / Q000473:pathology*; D007668:Kidney / Q000098:blood supply / Q000473:pathology*; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology*; D050356:Lipid Metabolism; D008297:Male; D008871:Microvilli / Q000378:metabolism / Q000473:pathology; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
D004075:Diglycerides; D005230:Fatty Acids, Nonesterified; D010743:Phospholipids; D014280:Triglycerides