Mlicrosomal Enzyme Induction, Lipoproteins and Atherosclerosis

Abstract

Abbreviations: HMGCoA = hydroxy-methyl glutaryl -coenzyme A HDL-C = high density lipoprotein cholesterol LDL=low density lipoprotein VLDL =very low density lipoprotein T-C = total cholesterol Atherosclerosis is the leading cause of death in modern societies. Hence a great effort has been devoted world-wide to the understanding and prevention of the atherosclerotic vascular process. Epidemiological, clinical and experimental investigations have demonstrated that lipoproteins are intimately linked with atherogenesis. They have shown that the extent and manifestation of atherosclerotic diseases, the most important of which are coronary heart disease and ischaemic cerebrovascular disease, are related to serum lipoprotein lipid and apoprotein concentrations. Some serum lipids and apoproteins are atherogenic while others seem to have an antiatherogenic effect. For this reason new possibilities to favourably influence serum lipid and apoprotein concentrations are of particular interest.Clinical investigations performed during the past ten years have demonstrated that serum lipoprotein levels are related to microsomal enzyme activity and lipid and protein concentrations in the liver. They have revealed that drugs and other compounds which induce microsomal enzymes may beneficially in proportion to the magnitude of induction influence serum lipid and apoprotein concentrations. These studies have thus implicated an approach to prevent the progress of atherosclerosis and the manifestations of its clinical consequences such as heart attacks, myocardial infarctions and strokes. This view is supported by experimental research indicating that an enzyme inducer can retard the cholesterol accumulation in the arterial wall and the formation of atherosclerotic plaque and also by epidemiological data suggesting a similar effect in man. This article will evaluate the effects of microsomal enzyme inducing agents on liver lipids and proteins and serum lipids and apoproteins as related to hepatic microsomal enzyme activity and to the microsomal enzyme induction, and further on the manifestation of atherosclerotic disease in man.

Evolution of Serum Lipids and Lipoprotein (a) Levels in Epileptic Children Treated With Carbamazepine, Valproic Acid, and Phenobarbital

“…43 On the basis of these studies, we can conclude that children treated with carbamazepine or phenobarbital are clearly at a higher risk than controls. 43 On the basis of these studies, we can conclude that children treated with carbamazepine or phenobarbital are clearly at a higher risk than controls.…”

“…40 Recently, it was reported that antiepileptic drug therapy with carbamazepine, phenobarbital, or valproic acid can increase the plasma levels of lipoprotein (a), and, subsequently, the risk of atherosclerotic vascular disease and thromboembolytic events [30][31][32] ; however, in the present study, there were no significant differences in mean lipoprotein (a) levels between the control group and the groups treated with carbamazepine and phenobarbital, whereas the group treated with valproic acid showed low levels of lipoprotein (a), and these results are in agreement with those reported by Verrotti et al 24 We do not have a plausible explanation for our results; on the basis of the microsomal enzyme-inducing properties of carbamazepine and phenobarbital, an increase in high-density lipoprotein cholesterol and a decrease in low-density lipoprotein cholesterol could be expected. [41][42][43] Nevertheless, the mere presence or absence of the enzyme-inducing effects of an individual antiepileptic drug does not seen to explain the changes observed in the lipid profile. In this sense, it was suggested that carbamazepine, phenobarbital, or phenytoin, even while increasing the cytochrome P-450 level, might compete with cholesterol in use of the enzyme, leading to a reduction in the transformation of cholesterol in biliary acids and, subsequently, to an increase in total cholesterol levels.…”

Carbohydrates, Alcohols, and Organic Acids

“…Catabolism of retinol is also accelerated. Finally, the induction of ethanol-metabolizing enzymes and various other liver proteins, including apolipoprotein A-I, affects synthesis and breakdown of lipids and lipoproteins (Luoma, 1988). Thus, increased omega-hydroxylation can change both type and rate of fatty acid metabolism (Laethem et al, 1993;Adas et al, 1998).…”

Possible Induction of Cholinesterase in Epileptic Patients Treated With Anticonvulsant Drugs: Relationship With Lipoprotein Levels

“…The effect of enzyme-inducing anticonvulsant drugs on serum concentrations of lipoproteins has been widely studied, both in children and in adults; [11][12][13][14][15][16][17][18][19] nevertheless, the influence of these drugs on atherosclerosis has been the subject of controversy. The increase of antiatherogenic high-density lipoproteins (HDL) and their relation to the degree of enzyme induction produced by these drugs has been well documented.…”

“…The increase of antiatherogenic high-density lipoproteins (HDL) and their relation to the degree of enzyme induction produced by these drugs has been well documented. [11][12][13][14][15]18 However, in individuals treated with anticonvulsant drugs, the development of a lipoprotein profile related to increased cardiovascular risk has also been indicated. 16,17,20 In this sense, if the induction of ChE by phenobarbital-type enzyme-inducing agents is confirmed, it should be expected that in epileptic patients treated with these drugs, there will be a direct relation between serum ChE activity and the atherogenic VLDL and LDL, as well as a reciprocal relation with HDL, as has been described for patients with diabetes, 6,21,22 hypertension, 23 and coronary artery disease.…”