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Effect of antioxidant vitamins and diets on hyperlipidemia and development of atherosclerosis in rabbits
Mom
IO October 1994: Foster Abstracts Lipmes
apolipoproteiu E, which are known to affect cell proliferation and cholesterol transport from the atherosclemtic lesion. 12281 w,
Cancer and hypocholesterolemin: tumor cells induce increased oxidative modification of LDL and enhanced LDL uptake bi non-hunor cells Wolfovitz E, Brook JG, Lipid Res. Lab., The Bruce
Rappaport Faculty of Med., Technion, Haga, Israel
Hypocholesterolemia has been reported in patients with disseminated cancer. The object of this study was to evaluate the effect of tumor cells on LDL oxidative modification and on LDL uptake by non-tumor cells. Both these processes could result in enhanced clearance of LDL from plasma. Oxidative edification of LDL (determined as rn~on~~dehyde formation) by MCF-7 tumor cells was 20% higher than in J774 macrophage-mediated LDL lipid peroxidation. Similarly, rat embryo fibmblasts, which had undergone tumor transformation owing to the presence of a ras protein mutation, induced an 8.5fold higher oxidative modification of LDL than did control tibroblasts. In addition, the fluidity of the LDL (measured by fluorescence polarization, using 1,6-diphenyl-1,3,5-hexatriene as the marker), incubated under oxidative stmss with MCF-7 cells, was 26% lower than LDL that was incubated with the J-774 macmphages under similar conditions. Conditioned medium (CM) obtained from the MCF-7 cells enhanced the degradation of LDL by J-774 macrophages by 58%, whereas CM obtained from nontumor cells in culture ((normal human skin fibmblasts (NHSF), smooth muscle cells @MC), and mouse peritoneal macmp~~s) did not affect the degradation of LDL. CM obtained from the rat ras mutant fibmblast stimulated LDL degradation by SMC and also by NHSF by 27% and 29%, respectively. Similarly, three plasma samples derived from patients with different malignancies doubled LDL degradation by J-774 macrophages in comparison to plasma derived from normal healthy volunteers. Thus, tumor cells may induce accelerated clearance of LDL due to stimulation of LDL oxidative modification, as well as enhance LDL degradation by non-malignant cells, and by so doing promote hypocholestemlemia.
Effect of antioxidant vitamins and diets on hyperlipidemia and development of atherosclerosis in rabbits Singh RB, Niaz MA, GfioshS. Ahmad S, Begum R, Ononchi Z, Ku~row FA, Heart Rex I.&., Morel, India
12291
20 rabbits fed a ~gh-sa~~-f~ diet were divided into group A, given also guava and papaya fruit (100 g/day) and vegetables and mustard oil (5 g/day); group B, supplemented with vitamins C and E (each 50 mg!day) and beta-carotene (10 mg/day); group C, which received an extra 10 g/day fat; and group D, receiving an extra 5 g/day fat, all for 36 weeks. After 12 weeks all the rabbits showed increased serum lipoproteins. Group A’s serum lipids
59
declined by 24 and 36 weeks whereas those in groups C and D continued to incmase. Levels of antioxidants increased in gmup A rabbits: at 36 weeks they were vit E 2.1, vit C 10.5, vit A 0.66 and carotene 0.08 cmov1, and they were even higher in group B. Lipid peroxides declined to 0.34 nmoyl at 36 weeks in group A but remained unchanged in groups C and D. Group B rabbits showed a rise in HDL-C and a greater decrease in lipid peroxides at 24 and 36 weeks. After stimulation of lipid pemxidation in all the rabbits, 3 in group C and 2 in group D died from comnary thrombosis whereas in gmups A and B no rabbit died. Aortic lipids and sudanophilia indicating atherosclerosis were significantly higher in groups C and D than A and B; fatty streaks, a~m~~us and fibrous plaques were noted in all group C and D rabbits, as well as intimal fibmsis and medial degeneration in group C. While group A and B rabbits showed minimal comnaq artery plaque size (36.424.4, 37.1 f4.2@m), group C and D were much larger (75.4 rt 10.6, 69.5 f 6.2pm). The same was true in the aorta. It seems possible that antioxidant and soluble fiber-rich diets, as well as antioxidant vitamins, can independently inhibit free radical generation, lipid pemxidation and atherogenesis. Plasma lipids and oxidative stress in HIV-infected patients Peuchant E, Dumon MF, Delmas_Beauvieux MC: Dubourg L, Thomas MJ, Constans J, Pellegiin JL. Sergeant C,‘Simonoff M, Conri C, Leng B, Clerc M, CHRU and CEN, Bordeaux, France
12301
Arterial thrombosis has been reported in some HIV-positive patients without any known a~roscle~sis risk factor. We have examined plasma lipids and oxidative stress in plasma and erythmcytes of 95 HIV-positive patients. divided into four groups accordin to their CD4 cell count. Group I (n = 32) had ~50 CD4/mm5 , Group II (n = 25) 50-200, Group III (n = 23) 2OC-400 and Group IV (n = 15) > 400 CD4/mm3. Compared to healthy controls (20 HIV-negative subjects), patients of groups I-III bad significantly higher higlycerides (P < 0.003) and Lp(a) (P < 0.004) and lower HDL-C (P c 0.001) and apo A-I (P < 0.0001). Moreover, the three groups of these patients had in plasma and erythrocytes a lower percentage of polyunsaturated acids (PUFA) than controls (P ~0.0001 and P < 0.02 respectively), correlated with more malondialdehyde (the end product of li~~mxidation) (P < 0.002). These values, cumbined with lower plasma levels of vitamin A (P < 0.0001) and selenium (P < O.@X),known ~tioxi~~, favor li~~mxid~on. The PUFA level also correlated with the CD4 cell count (P < 0.001) and apo A-I (P < O.OOOl),which suggests that lipoperoxidation is related both to evolution of the disease and to the decrease in ape A-I, the earliest abnormality that occurred in HIVpositive patients, with decrease in HDL-C. Antioxidant supplementation should be considered in HIV-positive patients; it may improve cell membrane function and act positively on the patient’s immune defenses.
LIPASES
(2311 w
Heparin-decasaccharide administration rapidly deptetes endothelinf stores of LPL and leads to impaired catabotfsm of ~yI~~c~ns Larnkjaer A, Hultin M, Ostergaard P, Oiivecmna T, I
Dept. of Med. Biochem. and Biop~s., Sweden
Univ. of Umed, Ume&
In this study, the effects of size-fractionated heparin on the release of lipoprotein lipase (LPL) and hepatic lipase (HL) were investigatea & vivo in-rats. Injection of hexasaccharides or octasaccharides (3.25 mgflcg body wt) led to very low LPL activities while the same dose of decasaccharides gave rise to activities represent-
ing -30% of those obtained with unfractionated heparin (UFH). However, LFL activity disappeared more rapidly from the circulation with decasaccharides than with UFH. This rapid clearance was partly explained by the inability of the deca.&charides to delay the hepatic uptake of f251-Iabeled LPL in a liver perfusion system. To explore the impact of the decasacchatide-mediated LPL depletion upon the metabolism of higlyceride-rich lipoproteins, in vivo doubly labeled ([‘4C]triglycerides-, [3H]retinyl ester-) chylomicrons were injected into rats before and after the decasaccl&ides. Triglyceride li olysis was delayed from 5 min (FCR 0.107 f 0.070 pools.min-! ns) to 2 h (FCR 0.065 f 0.017 pools.min-‘: P < 0.05) after the injection of decasaccharides, with
Atherosclerosis X, Montreal, October 1994
IO October 1994: Foster Abstracts Lipmes
apolipoproteiu E, which are known to affect cell proliferation and cholesterol transport from the atherosclemtic lesion. 12281 w,
Cancer and hypocholesterolemin: tumor cells induce increased oxidative modification of LDL and enhanced LDL uptake bi non-hunor cells Wolfovitz E, Brook JG, Lipid Res. Lab., The Bruce
Rappaport Faculty of Med., Technion, Haga, Israel
Hypocholesterolemia has been reported in patients with disseminated cancer. The object of this study was to evaluate the effect of tumor cells on LDL oxidative modification and on LDL uptake by non-tumor cells. Both these processes could result in enhanced clearance of LDL from plasma. Oxidative edification of LDL (determined as rn~on~~dehyde formation) by MCF-7 tumor cells was 20% higher than in J774 macrophage-mediated LDL lipid peroxidation. Similarly, rat embryo fibmblasts, which had undergone tumor transformation owing to the presence of a ras protein mutation, induced an 8.5fold higher oxidative modification of LDL than did control tibroblasts. In addition, the fluidity of the LDL (measured by fluorescence polarization, using 1,6-diphenyl-1,3,5-hexatriene as the marker), incubated under oxidative stmss with MCF-7 cells, was 26% lower than LDL that was incubated with the J-774 macmphages under similar conditions. Conditioned medium (CM) obtained from the MCF-7 cells enhanced the degradation of LDL by J-774 macrophages by 58%, whereas CM obtained from nontumor cells in culture ((normal human skin fibmblasts (NHSF), smooth muscle cells @MC), and mouse peritoneal macmp~~s) did not affect the degradation of LDL. CM obtained from the rat ras mutant fibmblast stimulated LDL degradation by SMC and also by NHSF by 27% and 29%, respectively. Similarly, three plasma samples derived from patients with different malignancies doubled LDL degradation by J-774 macrophages in comparison to plasma derived from normal healthy volunteers. Thus, tumor cells may induce accelerated clearance of LDL due to stimulation of LDL oxidative modification, as well as enhance LDL degradation by non-malignant cells, and by so doing promote hypocholestemlemia.
Effect of antioxidant vitamins and diets on hyperlipidemia and development of atherosclerosis in rabbits Singh RB, Niaz MA, GfioshS. Ahmad S, Begum R, Ononchi Z, Ku~row FA, Heart Rex I.&., Morel, India
12291
20 rabbits fed a ~gh-sa~~-f~ diet were divided into group A, given also guava and papaya fruit (100 g/day) and vegetables and mustard oil (5 g/day); group B, supplemented with vitamins C and E (each 50 mg!day) and beta-carotene (10 mg/day); group C, which received an extra 10 g/day fat; and group D, receiving an extra 5 g/day fat, all for 36 weeks. After 12 weeks all the rabbits showed increased serum lipoproteins. Group A’s serum lipids
59
declined by 24 and 36 weeks whereas those in groups C and D continued to incmase. Levels of antioxidants increased in gmup A rabbits: at 36 weeks they were vit E 2.1, vit C 10.5, vit A 0.66 and carotene 0.08 cmov1, and they were even higher in group B. Lipid peroxides declined to 0.34 nmoyl at 36 weeks in group A but remained unchanged in groups C and D. Group B rabbits showed a rise in HDL-C and a greater decrease in lipid peroxides at 24 and 36 weeks. After stimulation of lipid pemxidation in all the rabbits, 3 in group C and 2 in group D died from comnary thrombosis whereas in gmups A and B no rabbit died. Aortic lipids and sudanophilia indicating atherosclerosis were significantly higher in groups C and D than A and B; fatty streaks, a~m~~us and fibrous plaques were noted in all group C and D rabbits, as well as intimal fibmsis and medial degeneration in group C. While group A and B rabbits showed minimal comnaq artery plaque size (36.424.4, 37.1 f4.2@m), group C and D were much larger (75.4 rt 10.6, 69.5 f 6.2pm). The same was true in the aorta. It seems possible that antioxidant and soluble fiber-rich diets, as well as antioxidant vitamins, can independently inhibit free radical generation, lipid pemxidation and atherogenesis. Plasma lipids and oxidative stress in HIV-infected patients Peuchant E, Dumon MF, Delmas_Beauvieux MC: Dubourg L, Thomas MJ, Constans J, Pellegiin JL. Sergeant C,‘Simonoff M, Conri C, Leng B, Clerc M, CHRU and CEN, Bordeaux, France
12301
Arterial thrombosis has been reported in some HIV-positive patients without any known a~roscle~sis risk factor. We have examined plasma lipids and oxidative stress in plasma and erythmcytes of 95 HIV-positive patients. divided into four groups accordin to their CD4 cell count. Group I (n = 32) had ~50 CD4/mm5 , Group II (n = 25) 50-200, Group III (n = 23) 2OC-400 and Group IV (n = 15) > 400 CD4/mm3. Compared to healthy controls (20 HIV-negative subjects), patients of groups I-III bad significantly higher higlycerides (P < 0.003) and Lp(a) (P < 0.004) and lower HDL-C (P c 0.001) and apo A-I (P < 0.0001). Moreover, the three groups of these patients had in plasma and erythrocytes a lower percentage of polyunsaturated acids (PUFA) than controls (P ~0.0001 and P < 0.02 respectively), correlated with more malondialdehyde (the end product of li~~mxidation) (P < 0.002). These values, cumbined with lower plasma levels of vitamin A (P < 0.0001) and selenium (P < O.@X),known ~tioxi~~, favor li~~mxid~on. The PUFA level also correlated with the CD4 cell count (P < 0.001) and apo A-I (P < O.OOOl),which suggests that lipoperoxidation is related both to evolution of the disease and to the decrease in ape A-I, the earliest abnormality that occurred in HIVpositive patients, with decrease in HDL-C. Antioxidant supplementation should be considered in HIV-positive patients; it may improve cell membrane function and act positively on the patient’s immune defenses.
LIPASES
(2311 w
Heparin-decasaccharide administration rapidly deptetes endothelinf stores of LPL and leads to impaired catabotfsm of ~yI~~c~ns Larnkjaer A, Hultin M, Ostergaard P, Oiivecmna T, I
Dept. of Med. Biochem. and Biop~s., Sweden
Univ. of Umed, Ume&
In this study, the effects of size-fractionated heparin on the release of lipoprotein lipase (LPL) and hepatic lipase (HL) were investigatea & vivo in-rats. Injection of hexasaccharides or octasaccharides (3.25 mgflcg body wt) led to very low LPL activities while the same dose of decasaccharides gave rise to activities represent-
ing -30% of those obtained with unfractionated heparin (UFH). However, LFL activity disappeared more rapidly from the circulation with decasaccharides than with UFH. This rapid clearance was partly explained by the inability of the deca.&charides to delay the hepatic uptake of f251-Iabeled LPL in a liver perfusion system. To explore the impact of the decasacchatide-mediated LPL depletion upon the metabolism of higlyceride-rich lipoproteins, in vivo doubly labeled ([‘4C]triglycerides-, [3H]retinyl ester-) chylomicrons were injected into rats before and after the decasaccl&ides. Triglyceride li olysis was delayed from 5 min (FCR 0.107 f 0.070 pools.min-! ns) to 2 h (FCR 0.065 f 0.017 pools.min-‘: P < 0.05) after the injection of decasaccharides, with
Atherosclerosis X, Montreal, October 1994