The phospholipids of the hepatic endoplasmic reticulum. Structural change in liver injury

Abstract

Endoplasmic-reticulum phospholipids were measured during the first hour after carbon tetrachloride administration to male Sprague-Dawley rats and compared with carbon tetrachloride challenge of microsomes from control animals in vitro. The extracted lipids were separated by high-pressure liquid chromatography. No significant differences in the abundance of phosphatidylserine, phosphatidylethanolamine, phosphatidylinositol or phosphatidylcholine were found after either treatment when compared with untreated controls. Diene conjugate formation in each separated phospholipid was determined by measuring A(232) and expressed on the basis of lipid phosphorus. Phosphatidylserine was peroxidized 6-fold greater than in controls after challenge in vivo, reaching maximal change after 15min, whereas the other phospholipids showed little or no alteration. Fatty acid composition analysis was performed by g.l.c. after transesterification of individual phospholipids. Phosphatidylserine revealed two types of response: an abrupt decrease in relative abundance of oleic acid (C(18:1)) and linoleic acid (C(18:2)) without further loss and a slower, linear decrease in arachidonic acid (C(20:4)) over the first hour. Similar changes were not seen in other phospholipids. In the ;in vitro' model, the relative amounts of the phospholipids do not change. The extent of peroxidation was greater in all the phospholipids than found in vivo, with phosphatidylserine peroxidized to the greatest extent. These data suggest that carbon tetrachloride injury in vivo produces an early peroxidative event and that a specific phospholipid (phosphatidylserine) is selectively modified, although maintaining its relative concentration in the membrane. Dissection of this process in vitro will require refinement of existing systems to reduce the non-specific changes associated with the model system.

Fraxinus rhynchophylla ethanol extract attenuates carbon tetrachloride-induced liver fibrosis in rats via down-regulating the expressions of uPA, MMP-2, MMP-9 and TIMP-1

“…Polyunsaturated fatty acids (PUFAs) in membrane lipids are especially susceptible to free radical-initiated peroxidation (Svingen et al, 1979). PUFAs in phospholipids of the endothelium reticulum were decreased following in vivo CCl 4 administration (James et al, 1982). Liver fibrosis as well as the end-stage of liver fibrosis and cirrhosis represent the final common pathway of virtually all chronic liver diseases (Friedman, 2003).…”

Hepatoprotectant Ursodeoxycholyl Lysophosphatidylethanolamide Increasing Phosphatidylcholine Levels as a Potential Therapy of Acute Liver Injury

“…It was found nearly 50 years ago that carbon tetrachloride (CCl 4 ) intoxication is associated with changes in composition of PC and phosphatidylethanolamine (PE; Sgoutas, 1967 ; Shimizu, 1969 ; Sugano et al, 1970 ). Total phospholipids in hepatic microsomes (Sgoutas, 1967 ), endoplasmic reticulum (James et al, 1982 ), and plasma membrane (Camacho and Rubalcava, 1984 ) are markedly depressed following CCl 4 administration of experimental animals. This is due to decreased syntheses of both phospholipids and triglycerides readily observed 4–5 h after treatment (Gebhart and Brabec, 1985 ).…”

Esculetin Ameliorates Carbon Tetrachloride-Mediated Hepatic Apoptosis in Rats

“…Polyunsaturated fatty acids (PUFAs) in membrane lipids are especially susceptible to free radical-initiated peroxidation. PUFAs in phospholipids of the endothelium reticulum were decreased following CCl 4 administration in vivo [ 11 ]. Liver fibrosis as well as the end-stage of liver fibrosis and cirrhosis represents the final common pathway of virtually all chronic liver diseases [ 12 ].…”