Plasma high-density lipoproteins and hepatic microsomal enzyme induction

Abstract

The relationship between high-density lipoproteins (HDL) in plasma and hepatic structure and microsomal function has been investigated in 54 patients undergoing diagnostic liver biopsy. Plasma HDL cholesterol and major apoproteins were correlated with hepatic histology and microsomal enzyme activity assessed directly as liver cytochrome P-450 concentration and indirectly by plasma antipyrine clearance rate. HDL cholesterol, the concentrations of apoproteins A-I and A-II, the HDL cholesterol/total cholesterol ratio and cytochrome P-450 were low in subjects with moderate or severe hepatic fatty infiltration or cirrhosis when compared with the values for subjects with a normal live. HDL cholesterol and apoprotein A-I and the HDL cholesterol/total cholesterol ratio were directly proportional to the amount of non-fatty parenchyma in the livers. Subjects with a normal liver undergoing treatment with enzyme-inducing drugs, such as phenytoin, phenobarbital and primidone, had higher HDL cholesterol, apoproteins A-I and A-II, HDL cholesterol/total cholesterol ratio, cytochrome P-450 and antipyrine clearance rate than subjects not receiving such therapy. Treatment with inducers appeared to have compensated for the effect of liver disease in lowering plasma HLD. In the entire population, and also in subjects not taking inducing drugs, when considered separately, plasma HDL cholesterol, apoproteins A-I and A-II and the HDL cholesterol/total cholesterol ratio were significantly correlated with cytochrome P-450 concentration. In subjects on enzyme inducers, HDL cholesterol and apoprotein A-I levels and the HDL cholesterol/total cholesterol ratio were proportional to the magnitude of the induction. Serum triglycerides were inversely proportional to the measures of liver microsomal enzyme activity. The lipoprotein pattern, high HDL cholesterol and apoproteins A-I and A-II, and high HDL cholesterol/total cholesterol ratio that accompany microsomal induction are characterized by a reduced risk of atherosclerotic vascular disease and a prolonged expectation of life. The plasma changes presumably reflect the effect of enzyme inducers, such as phenytoin and phenobarbital on hepatic lipids and proteins.

Gene Activation, Apolipoprotein A‐I/High Density Lipoprotein, Atherosclerosis Prevention and Longevity

“…Clinical studies originating from the late 1970s associated microsomal induction with parallel increases in liver protein and phospholipid and serum apolipoprotein A-I and high density lipoprotein concentrations (Luoma 1979(Luoma & 1988Luoma et al 1979aLuoma et al , 1982aLuoma et al & 1983. They also suggested that induction stimulates the synthesis of apolipoprotein A-I and high density lipoprotein apolipoprotein-phospholipid complexes, causes an atherogenic change in the serum lipo-protein profile and can thus be exploited to treat atherosclerosis in humans.…”

“…Phenytoin treatment has been associated with elevated serum high density lipoprotein cholesterol and apolipoprotein A-I levels (Nikkila et al 1978;Luoma et al 1979b) and apolipoprotein A-I/A-I1 ratios (Luoma 1988). It may increase total cholesterol at the beginning of the therapy, but after a long period of treatment low or normal cholesterol and low density lipoprotein cholesterol levels have been observed (Fears 1986).…”

“…dietary factors, exposure to environmental chemicals including drugs, and inherited abnormalities in lipoprotein synthesis, and they may have beneficial or harmful health effects (LaPorte et al 198 I; Ehnholm et al 1982;Avogaro 1984;Fears 1986;Paoletti et al 1987). Several studies have demonstrated that drugs and other compounds which induce protein synthesis and activate genes in lipoprotein metabolism, may raise not only hepatic protein and phospholipid concentrations but also serum levels of high density lipoprotein cholesterol and apolipoprotein A-I, the major protein of high density lipoprotein, and the high density lipoprotein cholesterollcholesterol ratio (Luoma 1979(Luoma & 1988Luoma et al 1979aLuoma et al & 1982a. which are powerful protective factors against atherosclerotic vascular disease.…”

Intra-Individual Factors Affecting Lipid, Lipoprotein and Apolipoprotein Measurement: A Review

“…The effect on HDL metabolism is probably explained by two mechanisms, increased lipolysis of triglyceride-rich lipoproteins and induction of apolipoprotein synthesis in the liver. 87 Coffee Early epidemiological studies showed variable association between coffee and serum cholesterol concentrations and this led to the suggestion that these inconsistencies were due to differences in brewing methods." Most studies comparing caffeinated with decaffeinated coffee have shown no differences in concentrations of serum total and HDL-cholesterol, apoAI,89-91 apoB,89,91 or triglycerides.…”

Enzyme induction with rifampicin; lipoproteins and drug binding to alpha 1‐acid glycoprotein.

“…It has been suggested that the effect of phenobarbitone and phenytoin in raising HDL-cholesterol (Durrington, 1979;Nikkila et al, 1978) is also due to enzyme induction. In patients receiving these enzyme inducers plasma HDL concentrations are proportional to the magnitude of the induction assessed directly by liver cytochrome P-450 content and indirectly by plasma antipyrine clearance rate (Luoma et al, 1982). Rifampicin is the most potent enzyme inducer in man (Ohnhaus & Park, 1979) in routine clinical use.…”