Cholesterol-rich diets have different effects on lipid peroxidation, cholesterol oxides, and antioxidant enzymes in rats and rabbits.

The objective of this study was to compare the effect of cholesterol feeding of rats and rabbits. The levels of lipid peroxidation products and oxysterols in the plasma of the two species plus the antioxidant enzyme activities in the liver and erythrocytes were measured to explain their different susceptibilities to atherosclerosis. Our study showed that rats are less susceptible than are rabbits to the atherogenic effect of a cholesterol-rich diet because of differences in lipid peroxidation products as well as antioxidant enzymes activities in their livers. In rabbits, cholesterol feeding produced severe hypercholesterolemia (43-fold increase) and increased plasma and liver lipid peroxidation. Total as well as the individual oxysterol contents of 7alpha-, 7beta-hydroxycholesterol, alpha-epoxy, beta-epoxycholesterol, cholestanetriol, 7-keto, and 27-hydroxycholesterol significantly increased in the plasma of hypercholesterolemic (HC) rabbits. Erythrocyte glutathione peroxidase (GSH-Px) activity significantly decreased whereas catalase activity significantly increased in HC rabbits. In rats cholesterol feeding increased the plasma cholesterol only twofold and had no effect on plasma or liver lipid peroxidation. Only 7alpha- and 7beta-hydroxycholesterol increased and no change was observed in any of the antioxidant enzymes activity in the erythrocytes. Although cholesterol feeding caused a 10-fold increase of liver cholesterol as ester in both rats and rabbits, the antioxidant enzyme GSH-Px and catalase activities in the liver significantly increased in rats but significantly decreased in rabbits. The increase of GSH-Px and catalase activities in the liver of cholesterol fed rats could have a protective role against oxidation, thus preventing the formation of lipid peroxidation and oxysterols.

[1]  Andrew J. Brown,et al.  Oxysterols and atherosclerosis. , 1999, Atherosclerosis.

[2]  H. Abe,et al.  LIVER AND SERUM LIPID PEROXIDE LEVELS IN PATIENTS WITH LIVER DISEASES , 1982 .

[3]  J. C. van der Molen,et al.  Hydroxycholesterols in serum from hypercholesterolaemic patients with and without bile acid sequestrant therapy. , 1989, Clinica chimica acta; international journal of clinical chemistry.

[4]  S. Saito,et al.  EFFECTS OF DIETARY LIPIDS ON HEPATIC PROTEIN SYNTHESIS AND LIPID METABOLISM IN THE RAT. , 1965, The American journal of physiology.

[5]  Y. Sun,et al.  A simple method for clinical assay of superoxide dismutase. , 1988, Clinical chemistry.

[6]  L. Smith,et al.  Cholesterol autoxidation 1981-1986. , 1987, Chemistry and physics of lipids.

[7]  G. Ansari,et al.  Sterol metabolism. 44. Oxidation of cholesterol by dioxygen species , 2002 .

[8]  R. Burk,et al.  Glutathione peroxidase activity in selenium-deficient rat liver. , 1976, Biochemical and biophysical research communications.

[9]  I. Fridovich,et al.  Superoxide radical inhibits catalase. , 1982, The Journal of biological chemistry.

[10]  H. Kawano,et al.  Effect of cholesterol-rich diets with and without added vitamins E and C on the severity of atherosclerosis in rabbits. , 1997, The American journal of clinical nutrition.

[11]  K. Einarsson,et al.  On the possible use of the serum level of 7 alpha-hydroxycholesterol as a marker for increased activity of the cholesterol 7 alpha-hydroxylase in humans. , 1987, Journal of lipid research.

[12]  F. Kummerow,et al.  Cholesterol oxides in plasma and lipoproteins of magnesium-deficient rabbits and effects of their lipoproteins on endothelial barrier function. , 1994, Magnesium research.

[13]  T. Andersson,et al.  Dietary vitamin E increases the resistance to lipoprotein oxidation and attenuates endothelial dysfunction in the cholesterol-fed rabbit. , 1994, Atherosclerosis.

[14]  S. Juźwiak,et al.  Effect of selenium and vitamin E on the development of experimental atherosclerosis in rabbits. , 1991, Atherosclerosis.

[15]  I. Fridovich,et al.  Inactivation of glutathione peroxidase by superoxide radical. , 1985, Archives of biochemistry and biophysics.

[16]  J. Féher,et al.  Liver lipid peroxidation induced by cholesterol and its treatment with a dihydroquinoline type free radical scavenger in rabbits. , 1984, Acta physiologica Hungarica.

[17]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[18]  J. Cuthbert,et al.  Regulation of hepatic sterol metabolism in the rat. Parallel regulation of activity and mRNA for 7 alpha-hydroxylase but not 3-hydroxy-3-methylglutaryl-coenzyme A reductase or low density lipoprotein receptor. , 1992, The Journal of biological chemistry.

[19]  P. Barter,et al.  Secretion of cholesteryl ester-enriched very low density lipoproteins by the liver of cholesterol-fed rabbits. , 1985, Atherosclerosis.

[20]  J. Watson,et al.  Enzymic assay of glycerol, dihydroxyacetone, and glyceraldehyde. , 1967, Archives of biochemistry and biophysics.

[21]  Hans Ulrich Bergmeyer,et al.  Methods of Enzymatic Analysis , 2019 .

[22]  J. Gaziano,et al.  Content of antioxidants, preformed lipid hydroperoxides, and cholesterol as predictors of the susceptibility of human LDL to metal ion-dependent and -independent oxidation. , 1993, Journal of lipid research.

[23]  八木 国夫.  Lipid peroxides in biology and medicine , 1982 .

[24]  G. Tint,et al.  Regulation of classic and alternative bile acid synthesis in hypercholesterolemic rabbits: effects of cholesterol feeding and bile acid depletion. , 1998, Journal of lipid research.

[25]  K. Yagi,et al.  A simple fluorometric assay for lipoperoxide in blood plasma. , 1976, Biochemical medicine.

[26]  C. B. Taylor,et al.  Spontaneously occurring angiotoxic derivatives of cholesterol. , 1979, The American journal of clinical nutrition.

[27]  J. Folch,et al.  A simple method for the isolation and purification of total lipides from animal tissues. , 1957, The Journal of biological chemistry.

[28]  N. Heintz,et al.  Differential regulation of antioxidant enzymes in response to oxidants. , 1991, The Journal of biological chemistry.

[29]  A. Simon,et al.  Erythrocyte antioxidant status in asymptomatic hypercholesterolemic men. , 1997, Atherosclerosis.

[30]  B. Hennig,et al.  Effect of oxysterol-enriched low-density lipoprotein on endothelial barrier function in culture. Low-density lipoproteins. , 1991, Annals of nutrition & metabolism.

[31]  J. Albers,et al.  Dextran sulfate-Mg2+ precipitation procedure for quantitation of high-density-lipoprotein cholesterol. , 1982, Clinical chemistry.

[32]  Margaret S. Wu,et al.  Low density lipoprotein is protected from oxidation and the progression of atherosclerosis is slowed in cholesterol-fed rabbits by the antioxidant N,N'-diphenyl-phenylenediamine. , 1992, The Journal of clinical investigation.

[33]  E. Rice.  Rapid determination of total hemoglobin as hemiglobin cyanide in blood containing carboxyhemoglobin. , 1967, Clinica chimica acta; international journal of clinical chemistry.

[34]  D. Greenblatt,et al.  Increased bile acid pool inhibits cholesterol 7 alpha-hydroxylase in cholesterol-fed rabbits. , 1997, Gastroenterology.

[35]  B. Hu,et al.  Angiotoxicity and atherogenicity of cholesterol oxides , 1991, Journal of clinical laboratory analysis.

[36]  I. Björkhem,et al.  Use of an 18O2 Inhalation Technique and Mass Isotopomer Distribution Analysis to Study Oxygenation of Cholesterol in Rat , 1995, The Journal of Biological Chemistry.

[37]  C. B. Taylor,et al.  Cholesterol oxidation derivatives and arterial endothelial damage. , 1985, Atherosclerosis.

[38]  I. Akkuş,et al.  Investigation of erythrocyte membrane lipid peroxidation and antioxidant defense systems of patients with coronary artery disease (CAD) documented by angiography. , 1996, Clinica chimica acta; international journal of clinical chemistry.

[39]  L. Beilin,et al.  Dietary oxysterols are incorporated in plasma triglyceride-rich lipoproteins, increase their susceptibility to oxidation and increase aortic cholesterol concentration of rabbits. , 1998, Journal of lipid research.

[40]  A. C. Tsai,et al.  Lipid peroxidation and glutathione peroxidase activity in the liver of cholesterol-fed rats. , 1975, The Journal of nutrition.

[41]  M. Sugano,et al.  Dietary oxidized cholesterol modulates cholesterol metabolism and linoleic acid desaturation in rats fed high-cholesterol diets , 1998, Lipids.

[42]  L. Smith,et al.  Another cholesterol hypothesis: cholesterol as antioxidant. , 1991, Free radical biology & medicine.

[43]  A. Sevanian,et al.  Arterial injury by cholesterol oxidation products causes endothelial dysfunction and arterial wall cholesterol accumulation. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[44]  J. Milner,et al.  Improved method for selenium determination in biological samples by gas chromatography. , 1981, Journal of chromatography.

[45]  K. Yagi.  Lipid peroxides and human diseases. , 1987, Chemistry and physics of lipids.

[46]  G. Schroepfer,et al.  Synergistic action of two oxysterols in the lowering of HMG-CoA reductase activity in CHO-K1 cells. , 1992, Biochemical and biophysical research communications.

[47]  I. Björkhem,et al.  On the mechanism of stimulation of cholesterol 7α-hydroxylase by dietary cholesterol , 1991 .

[48]  P. Fu,et al.  Enzymatic determination of total serum cholesterol. , 1974, Clinical chemistry.

[49]  K. Prasad,et al.  Antioxidant enzymes in hypercholesterolemia and effects of vitamin E in rabbits. , 1993, Atherosclerosis.

[50]  G Bucolo,et al.  Quantitative determination of serum triglycerides by the use of enzymes. , 1973, Clinical chemistry.

[51]  K. Feingold,et al.  Oxidized cholesterol in the diet accelerates the development of aortic atherosclerosis in cholesterol-fed rabbits. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[52]  R. Dean,et al.  Free and esterified oxysterol: formation during copper-oxidation of low density lipoprotein and uptake by macrophages. , 1996, Journal of lipid research.

[53]  B. Zak,et al.  Rapid estimation of free and total cholesterol. , 1954, American journal of clinical pathology.

[54]  B. Halliwell.  Mechanisms involved in the generation of free radicals. , 1996, Pathologie-biologie.

[55]  A. Diplock,et al.  Glutathione peroxidase (EC 1.11.1.9), glutathione-S-transferase (EC 2.5.1.13), superoxide dismutase (EC 1.15.1.1) and catalase (EC 1.11.1.6) activities in tissues of ducklings deprived of vitamin E and selenium , 1983, British Journal of Nutrition.

[56]  C. B. Taylor,et al.  Angiotoxicity and arteriosclerosis due to contaminants of USP-grade cholesterol. , 1976, Archives of pathology & laboratory medicine.

[57]  W. Valentine,et al.  Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. , 1967, The Journal of laboratory and clinical medicine.

[58]  G. Ness,et al.  Differing effects of cholesterol and taurocholate on steady state hepatic HMG-CoA reductase and cholesterol 7 alpha-hydroxylase activities and mRNA levels in the rat. , 1992, Journal of lipid research.