RESUMEN
OBJECTIVE: Oral contraceptive formulations can alter plasma lipid and lipoprotein levels; however, lower-dose triphasic tablets show only minimal metabolic effects during 6 or 12 cycles of use. Involvement of lipids in chronic cardiovascular conditions, plus long-term use of oral contraceptive tablets, prompted this first 24-cycle study of the effect of triphasic formulations on young women. METHODS: 69 women assigned randomly to an ethinyl estradiol/levonorgestrel formulation (Triphasil) or an ethinyl estradiol/norethindrone formulation (Ortho 7/7/7) and 25 control women (no hormonal contraception) had blood sampled for lipids and lipoproteins pre-trial, and at 3- or 6-cycle intervals for 24 cycles. RESULTS: At cycle 24, control women experienced no significant change from baseline in any variable except apolipoprotein B (apo B). Plasma apo B increased 42% (P < .01), reflecting the LDL apo B increase (42%, P < .01). Both combination formulations significantly increased apo B (plasma, VLDL, IDL and LDL); the increases ranged between 47% and 84%. Plasma apo A1 rose (15%, P < .001) in the Ortho 7/7/7 group only. Plasma and LDL triglycerides were increased significantly (P < .001) by the norethindrone product, 43% and 81%, respectively, and plasma and LDL cholesterol, 14% and 28%, respectively. Cholesterol decreased in all other subfractions, including HDL (11%, P < .01). HDL cholesterol decreased significantly in the Triphasil group (8%, P < .05); no other cholesterol subfractions changed significantly. All cycle-24 lipid and lipoprotein values remained well within respective normal ranges. CONCLUSION: Although 2-year exposure to the triphasic oral contraceptive formulations changed the lipid risk factors for cardiovascular disease only within normal ranges, there remains potential for long-term health effects when compounded with other risk factors.
PIP: The first 24-cycle study of the metabolic effects of triphasic oral contraceptives (OCs) recorded significant changes in lipid values, yet none of these values moved outside the normal range. Included in the study were 69 non-smoking Canadian women 19-29 years of age with no history of obesity, diabetes, or alcohol misuse. Subjects were randomly assigned to receive either an ethinyl estradiol-norethindrone formulation (Ortho 7/7/7) or an ethinyl estradiol-levonorgestrel preparation (Triphasic). 25 controls underwent periodic blood samplings for lipid and lipoprotein levels. The only significant change recorded among controls was a 42% increase in the plasma apo B level resulting from changes in the low density lipoprotein (LDL) apo B subfraction. In the Ortho 7/7/7 and Triphasic groups, both plasma and LDL triglycerides were increased above baseline and above values for controls at the 24-month point. In Ortho 7/7/7 acceptors, LDL cholesterol increased by 28%, high density lipoprotein (HDL) decreased by 11%, and plasma cholesterol increased by 14%; other cholesterol levels decreased significantly. In the Triphasic group, HDL decreased by 8%, but no other significant changes occurred. Apo A1 increased by 15% in the Ortho 7/7/7 group, but not among Triphasic users; all apo B values increased significantly in both treatment groups. Although these changes in lipid profiles among triphasic OC users do not seem to increase the risk of cardiovascular disease, there is potential for adverse health effects when other cardiovascular risk factors, especially smoking, are present.
Asunto(s)
Anticonceptivos Orales Combinados/farmacología , Anticonceptivos Hormonales Orales/farmacología , Anticonceptivos Sintéticos Orales/farmacología , Etinilestradiol/farmacología , Lípidos/sangre , Noretindrona/farmacología , Norgestrel/farmacología , Adolescente , Adulto , Apolipoproteína A-I/sangre , Apolipoproteína A-I/efectos de los fármacos , Apolipoproteínas B/sangre , Apolipoproteínas B/efectos de los fármacos , Colesterol/sangre , HDL-Colesterol/sangre , HDL-Colesterol/efectos de los fármacos , LDL-Colesterol/sangre , LDL-Colesterol/efectos de los fármacos , Combinación de Medicamentos , Combinación Etinil Estradiol-Norgestrel , Femenino , Humanos , Lipoproteínas/sangre , Lipoproteínas/efectos de los fármacos , Lipoproteínas LDL/sangre , Lipoproteínas LDL/efectos de los fármacos , Lipoproteínas VLDL/sangre , Lipoproteínas VLDL/efectos de los fármacos , Factores de Riesgo , Triglicéridos/sangreRESUMEN
Inbred mouse strains vary in susceptibility or resistance to dietary induced atherosclerosis. To investigate the effect of polyunsaturated fat feeding on postprandial serum cholesterol levels, in C57BL/67 (B6) and BALB/cJ inbred mice, we fed by stomach gavage previously fasted mice, a mixture containing 30% sunflower oil, 5% cholesterol, 2% sodium cholate and 0.5% choline chloride. The most significant difference in serum cholesterol levels between B6 and BALB/cJ mouse strains was observed at 2 h postfeeding. Susceptible B6 strain mice had a 41% postprandial increment in serum cholesterol. The resistant BALB/cJ strain had an insignificant 16% rise in serum cholesterol, at 2 h. We next examined eight other inbred mouse strains, to identify the gene(s) that regulate the observed 2 h postprandial hypercholesterolemia response, in the susceptible B6 mouse strain. Only the C57BR/cdJ and C57L/J strains developed postprandial hypercholesterolemia, at 2 h. The C57BR/cdJ strain had a 20% increase and the C57L/J strain a 62% increase in postprandial serum cholesterol levels. From this result, we found that the postprandial hypercholesterolemic response to an acute polyunsaturated fat-cholesterol feed, cosegregated with the a allele at the Gpd-1 and Ahd-1 loci, on mouse chromosome 4. In this study, non-responsiveness cosegregated with the b allele at the Gpd-1 and Ahd-1 loci. Thus polyunsaturated fat-cholesterol induced postprandial hypercholesterolemia appeared to be genetically determined by a gene located between the Gpd-1 and Ahd-1 loci, in mice. The putative gene regulating polyunsaturated fat-cholesterol induced post-absorptive hypercholesterolemia was designated Phc-2.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Hipercolesterolemia/genética , Animales , Colesterol/sangre , Colesterol en la Dieta/administración & dosificación , Mapeo Cromosómico , Cromosomas , Cromosomas Humanos Par 1 , Grasas Insaturadas en la Dieta/administración & dosificación , Humanos , Hipercolesterolemia/metabolismo , Masculino , Ratones , Ratones EndogámicosRESUMEN
This study assessed serum lipid, lipoprotein and apolipoprotein changes during one year in 3 groups of nonsmoking women: 1) Triphasil(R); 2) Ortho(R) 7/7/7; 3) Controls. Both oral contraceptives contain the estrogen, ethinyl estradiol(EE), in combination with a progestin in three different ratios during each cycle. The progestin in Triphasil is d-norgestrel, as the dl-racemate norgestrel (NG), whereas that in Ortho 7/7/7 is norethindrone(NE). Total plasma triglycerides were elevated significantly from baseline (p < 0.001) with Ortho 7/7/7 at 3, 6 and 12 months, but only at 3 months with Triphasil, p = 0.047. Triglycerides were elevated in the LDL fraction with Ortho 7/7/7 at 3 months (p = 0.001), 6 months (p = 0.018) and 12 months (p = 0.010). In contrast, LDL triglycerides were not significantly elevated with Triphasil. Similarly, IDL triglycerides were elevated only in the Ortho 7/7/7 group at 6 months (p = 0.002) and 12 months (p = 0.001). Plasma cholesterol was elevated only in the Ortho 7/7/7 group at 3, 6 and 12 months with p values of 0.009, 0.005 and 0.010, respectively. Cholesterol in the LDL fraction was elevated with Ortho 7/7/7 at 12 months (p = 0.002). Plasma apolipoprotein B (apo B) increased at least 24% from baseline for both the Triphasil and Ortho 7/7/7 groups at 3 and 12 months (p < 0.001). However, at 6 months, apolipoprotein B increased only 17.7% (p = 0.008) with Triphasil compared to 29.7% (p < 0.001) with Ortho 7/7/7 at 6 months. Apo B was increased (p < 0.001) in LDL with Triphasil at 3 months only, whereas LDL apo B was increased at 3, 6 and 12 months with Ortho 7/7/7 (p < 0.001, p = 0.020 and p = 0.012, respectively). Apo B increased dramatically in the IDL fraction of both oral contraceptive user populations, with the range of increases being between 48% and 87% during the year (p < 0.001 at all times). Significant elevations in VLDL apo B ranged from 71% to 106% (p < 0.001) with Triphasil and from 42.4% (p < 0.005) to 72.6% (p < 0.001) with Ortho 7/7/7. In conclusion, norethindrone- and dl-norgestrel-formulations have divergent effects on several components of plasma lipoprotein and lipid metabolism, but both products increase plasma and IDL apo B.
Asunto(s)
Anticonceptivos Sintéticos Orales/farmacología , Etinilestradiol/farmacología , Metabolismo de los Lípidos , Noretindrona/farmacología , Norgestrel/farmacología , Administración Oral , Adolescente , Adulto , Apolipoproteínas B/sangre , Colesterol/sangre , Anticonceptivos Orales Combinados/administración & dosificación , Anticonceptivos Orales Combinados/farmacología , Anticonceptivos Sintéticos Orales/administración & dosificación , Combinación de Medicamentos , Etinilestradiol/administración & dosificación , Combinación Etinil Estradiol-Norgestrel , Femenino , Humanos , Lípidos/sangre , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Lipoproteínas VLDL/sangre , Noretindrona/administración & dosificación , Norgestrel/administración & dosificación , Triglicéridos/sangreRESUMEN
Male Wistar rats were injected intravenously with 2 mL of Intralipid containing 7.5 x 10(5) counts per minute (cpm) [14C]cholesterol and 7.5 x 10(5) cpm beta-[3H]sitosterol. Blood was withdrawn immediately and at 5, 10, 20, 60, 120, and 1440 min after injection from different animals. Plasma and red cells were separated and washed by conventional centrifugation, while lipoprotein density classes corresponding to chylomicrons, very low (VLDL), low (LDL), and high density lipoproteins (HDL) were isolated by ultracentrifugation. Total lipid and sterol compositions were determined by thin-layer chromatography in combination with gas-liquid chromatography, whereas radioactivity was measured by scintillation counting. The ratio of [14C]cholesterol/beta-[3H]sitosterol rose from 1 to 3.65 in the plasma VLDL fraction, whereas that in the LDL and HDL fractions were equilibrated at about 2, following an initial transient increase in favour of cholesterol. The appearance and disappearance of the radioactivity from LDL and HDL fractions exhibited precursor-product relationship owing probably to the conversion of the Intralipid into an intermediate lipoprotein-X-like particle, which possesses a density similar to that of LDL. The radioactive cholesterol and beta-sitosterol were incorporated into the red blood cell membranes at nearly similar initial rates, while at later times the incorporation of cholesterol was much preferred.
Asunto(s)
Colesterol/sangre , Eritrocitos/metabolismo , Emulsiones Grasas Intravenosas/farmacocinética , Lipoproteínas/sangre , Sitoesteroles/sangre , Animales , Lípidos/análisis , Masculino , Microscopía Electrónica , Ratas , Ratas Endogámicas , Esteroles/metabolismoRESUMEN
In normal subjects, apolipoprotein E (apo E) is present on very low density lipoproteins (VLDL) (fraction I) and on particles of a size intermediate between VLDL and low density lipoproteins (LDL) (fraction II). The major portion of apo E is, however, on particles smaller than LDL but larger than the average high density lipoproteins (HDL) (fraction III). To investigate the possible role of the vascular lipases in determining this distribution of apo E among the plasma lipoproteins, we studied subjects with primary deficiency of either hepatic lipase or of lipoprotein lipase and compared them with normal subjects. Subjects with familial hepatic triglyceride lipase deficiency (n = 2) differ markedly from normal in that fraction II is the dominant apo E-containing group of lipoproteins. When lipolysis of VLDL was enhanced in these subjects upon release of lipoprotein lipase by intravenous heparin, a shift of the apo E from VLDL into fractions II and III was observed. In contrast, apolipoproteins CII and CIII (apo CII and CIII, respectively) did not accumulate in intermediate-sized particles but were shifted markedly from triglyceride rich lipoproteins to HDL after treatment with heparin. In subjects with primary lipoprotein lipase deficiency (n = 4), apo E was confined to fractions I and III. Release of hepatic triglyceride lipase by heparin injection in these subjects produced a shift of apo E from fraction I to III with no significant increase in fraction II. This movement of apo E from large VLDL and chylomicron-sized particles occurred with little hydrolysis of triglyceride and no significant shift of apo CII or CIII into HDL from triglyceride rich lipoproteins. When both lipoprotein lipase and hepatic triglyceride lipase were released by intravenous heparin injection into normal subjects (n = 3), fraction I declined and the apo E content of fraction III increased by an equivalent amount. Either moderate or no change was noted in the intermediate sized particles (fraction II). These data strongly support the hypothesis that fraction II is the product of the action of lipoprotein lipase upon triglyceride rich lipoproteins and is highly dependent on hepatic triglyceride lipase for its further catabolism. In addition, the hydrolysis by hepatic triglyceride lipase of triglyceride rich lipoproteins in general results in a preferential loss of apo E and its transfer to a specific group of large HDL.
Asunto(s)
Apolipoproteínas E/sangre , Heparina/farmacología , Hiperlipoproteinemia Tipo I/sangre , Hiperlipoproteinemias/sangre , Lipasa/deficiencia , Adulto , Preescolar , Femenino , Humanos , Hiperlipoproteinemia Tipo IV/sangre , Hiperlipoproteinemia Tipo V/sangre , Lipólisis/efectos de los fármacos , Lipoproteínas/sangre , Lipoproteínas/clasificación , Hígado/enzimología , Masculino , Persona de Mediana EdadRESUMEN
Two previously unidentified apolipoproteins (apo) designated apo C-II-X and C-II-Y have been found in plasma of homozygotes and obligate heterozygotes of a family with apo C-II deficiency. Because the plasma of homozygotes do not activate lipoprotein lipase, apo C-II-X and C-II-Y are apparently nonfunctional. These apolipoproteins have isoelectric focusing points of 5.15 and 5.54, respectively, compared with 4.88 and 4.74 for the known isomorphs, C-II-1 and C-II-2, respectively. They have approximately similar molecular weights to apo C-II-1 and C-II-2 on two-dimensional sodium dodecyl sulphate-glycerol-polyacrylamide slab gel electrophoresis. They do not form insoluble antigen-antibody complexes with antibodies to apo C-II in single antibody immunodiffusion or electroimmunoassay systems. However, using a double-antibody technique in which immunoblotting is coupled with polyacrylamide isoelectric focusing slab gel electrophoresis, apo C-II-1, C-II-2, C-II-X, and C-II-Y have similar reactivity with antibodies to apo C-II. In this family the presence of apo C-II-X and C-II-Y discriminates obligate heterozygotes from normal subjects.
Asunto(s)
Apolipoproteínas C/deficiencia , Apolipoproteína C-II , Apolipoproteínas C/genética , Activación Enzimática , Femenino , Heterocigoto , Homocigoto , Humanos , Técnicas de Inmunoadsorción , Focalización Isoeléctrica , Lipoproteína Lipasa/sangre , Lipoproteínas VLDL/sangre , Masculino , MutaciónRESUMEN
One hundred sixty-nine healthy women, aged 17 to 29 years, nonsmokers or light smokers (fewer than ten cigarettes per day), were assigned randomly to take one of five oral contraceptives: 1) 100 micrograms mestranol plus 0.5 mg ethynodiol diacetate (100 M + 0.5 ED); 2) 100 micrograms mestranol plus 1.0 mg ethynodiol diacetate (100 M + 1.0 ED); 3) 50 micrograms ethinyl estradiol plus 1.0 mg ethynodiol diacetate (50 EE + 1.0 ED); 4) 30 micrograms ethinyl estradiol plus 2.0 mg ethynodiol diacetate (30 EE + 2.0 ED); or 5) 30 micrograms ethinyl estradiol plus 0.15 mg levonorgestrel (30 EE + 0.15 NG). One hundred forty-seven women completed the study. When assessed for within-group differences, all preparation caused a statistically significant increase in total triglyceride (from 17.0 to 46.4 mg/dL), total cholesterol (from 6.3 to 24.4 mg/dL), and low-density lipoprotein (LDL) cholesterol (from 7.0 to 10.3 mg/dL). Effects on high-density lipoprotein (HDL) cholesterol varied widely. The product 100 M + 0.5 ED markedly increased (9.9 mg/dL) HDL cholesterol. Neither 100 M + 1.0 ED nor 50 EE + 1.0 ED altered HDL cholesterol levels, whereas both preparations containing 30 micrograms estrogen showed decreases: the preparation containing 2.0 mg ethynodiol diacetate lowered HDL cholesterol by 3.6 mg/dL and that containing 0.15 mg levonorgestrel lowered it by 6.9 mg/dL. Specific between-group comparisons revealed no statistically significant differences between differing amounts of estrogen (50 EE + 1.0 ED versus 100 M + 1.0 ED).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Colesterol/sangre , Anticonceptivos Orales/farmacología , Lipoproteínas/sangre , Triglicéridos/sangre , Adolescente , Adulto , Anticonceptivos Orales Combinados/farmacología , Etinilestradiol/farmacología , Diacetato de Etinodiol/farmacología , Femenino , Humanos , Levonorgestrel , Lípidos/sangre , Mestranol/farmacología , Norgestrel/farmacologíaRESUMEN
Male Wistar rats were infused intravenously with various amounts (2-20 mL/24 h) of Intralipid or Intralipid containing cholesterol or plant sterols (5-100 mg/24h), and hepatic cholesterogenesis was monitored by measuring the incorporation of [1-14C]acetate into the nonsaponifiable sterols of liver slices. It was observed that the infusion of Intralipid alone resulted in a hypercholesterolemia that varied with the amount of Intralipid administered and that it was accompanied by up to a threefold increase in hepatic cholesterogenesis. Inclusion of cholesterol in the Intralipid at 5 mg/mL prevented the increase in hepatic cholesterol biosynthesis, while an inhibition of up to 95% of control synthesis was achieved when a total of 33 mg of cholesterol in 20 mL Intralipid was infused over a 24-h period. It is concluded that the feedback regulation of cholesterol biosynthesis is operative even when the entry of cholesterol bypasses the intestine and the lipoprotein synthesis taking place there and that Intralipid is a suitable medium for the intravenous introduction of a large mass of metabolically active cholesterol molecules. Similar infusions of mixed plant sterols failed to prevent the activation or inhibition of cholesterol biosynthesis, but the administration of much larger doses of plant sterols (100 mg) brought about a partial inhibition of hepatic cholesterogenesis. It is concluded that the presence of an alkyl group in the side chain prevents the plant sterols from an effective interaction with the critical sites of the feedback regulatory system of cholesterogenesis. The effects of the larger doses of plant sterols were attributed to the displacement of increasing amounts of free cholesterol from the vascular tissues, which resulted in an effective elevation of plasma cholesterol levels. The infusion of either cholesterol or plant sterols over the 24-h period did not appear to have a consistent effect upon the composition or secretion of biliary bile acids.
Asunto(s)
Colesterol/administración & dosificación , Emulsiones Grasas Intravenosas/administración & dosificación , Hígado/metabolismo , Esteroles/administración & dosificación , Acetatos/metabolismo , Animales , Radioisótopos de Carbono , Colesterol/biosíntesis , Colesterol/farmacología , Cromatografía de Gases/métodos , Emulsiones Grasas Intravenosas/farmacología , Infusiones Parenterales , Hígado/efectos de los fármacos , Masculino , Microsomas Hepáticos/metabolismo , Ratas , Ratas Endogámicas , Esteroles/biosíntesisAsunto(s)
Lipasa/metabolismo , Errores Innatos del Metabolismo Lipídico/genética , Lipoproteína Lipasa/metabolismo , Lipoproteínas/sangre , Hígado/metabolismo , Adulto , Apolipoproteínas/sangre , Colesterol/sangre , Ésteres del Colesterol/sangre , LDL-Colesterol , VLDL-Colesterol , Femenino , Humanos , Errores Innatos del Metabolismo Lipídico/sangre , Lipólisis , Lipoproteínas LDL/sangre , Lipoproteínas VLDL/sangre , Masculino , Triglicéridos/sangreAsunto(s)
Conductos Biliares Intrahepáticos/efectos de los fármacos , Colesterol/fisiología , Ácido Litocólico/farmacología , Hígado/ultraestructura , Lípidos de la Membrana/fisiología , Animales , Bilis/efectos de los fármacos , Membrana Celular/enzimología , Colestasis/inducido químicamente , Lípidos/análisis , Hígado/citología , Masculino , Microscopía Electrónica , Pentobarbital/farmacología , Ratas , ATPasa Intercambiadora de Sodio-Potasio/metabolismoAsunto(s)
Colestasis Intrahepática/inducido químicamente , Ácidos Cólicos/uso terapéutico , Ácido Litocólico/efectos adversos , Hígado/efectos de los fármacos , Albúminas/farmacología , Animales , Bilis/efectos de los fármacos , Membrana Celular/efectos de los fármacos , Membrana Celular/enzimología , Colestasis Intrahepática/prevención & control , Colesterol/metabolismo , Ácidos Cólicos/metabolismo , Ácido Deshidrocólico/farmacología , Ácido Litocólico/metabolismo , Hígado/ultraestructura , Masculino , Fosfolípidos/metabolismo , Ratas , Ácido Taurocólico/farmacologíaRESUMEN
Fasting rats were infused with 10% Intralipid for 24 h (0.33 mL/h per 100 g body weight) and the plasma lipoproteins isolated and compared with those of fed animals and animals with bile duct ligatures as controls. There was a 6- to 10-fold increase in the free cholesterol and phospholipid content of total plasma in animals infused with Intralipid or with ligated bile ducts. The changes were largely restricted to the low density lipoproteins (d=1.019--1.063 g/mL) where free cholesterol and phospholipid increased 30- to 60-fold compared with fed control animals. Hydroxylapatite chromatography of the low density lipoprotein fractions of both Intralipid-infused and bile duct ligated animals yielded a subfraction which was rich in free cholesterol (27%), phosphatidylcholine (66%), and protein (6%); the latter was composed primarily of albumin and apo C proteins. The electrophoretic mobility and polyanionic precipitation properties of the abnormal lipoprotein were indistinguishable from those of lipoprotein X isolated from the animals with bile duct ligatures. The albumin in the abnormal lipoprotein from both groups of experimental animals was detected immunochemically only after delipidation of the lipoprotein. Twice as much of the lipoprotein X accumulated in Intralipid-infused than in the bile duct ligated animals. On rechromatography of the residual low density lipoprotein other subfractions could be isolated which possessed lipid and protein proportions intermediate between those of the lipoprotein X and of normal rat plasma low density lipoprotein. The activity of lecithin cholesterol acyl transferase was increased twofold in the Intralipid-infused animals when compared with control animals, but it decreased by 50% in the animals with bile duct ligatures. It is concluded that the unusual lipoprotein X accumulates in the plasma of Intralipid-infused animals owing to incomplete clearance of the exogenous phospholipid, which mobilized tissue cholesterol and in the form of vesicular particles serves as a lipid phase for apo C proteins. A comparable mechanism is suggested for the formation of lipoprotein X in the animals with bile duct ligature.
Asunto(s)
Emulsiones Grasas Intravenosas/farmacología , Lipoproteínas/sangre , Animales , Colesterol/análisis , Colesterol/sangre , Inmunodifusión , Masculino , Peso Molecular , Fosfolípidos/análisis , Fosfolípidos/sangre , Ratas , Triglicéridos/sangreAsunto(s)
Colestasis/inducido químicamente , Ácido Litocólico , Hígado/efectos de los fármacos , Ácido Taurolitocólico , Adenosina Trifosfatasas/metabolismo , Animales , Bilis/metabolismo , Conductos Biliares Intrahepáticos/efectos de los fármacos , Conductos Biliares Intrahepáticos/metabolismo , Conductos Biliares Intrahepáticos/ultraestructura , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Membrana Celular/ultraestructura , Colestasis/etiología , Colestasis/patología , Colesterol/metabolismo , Modelos Animales de Enfermedad , Ácido Litocólico/análogos & derivados , Hígado/metabolismo , Hígado/ultraestructura , Masculino , Proteínas de la Membrana/metabolismo , Péptidos/metabolismo , Fosfolípidos/metabolismo , Ratas , Tasa de Secreción , ATPasa Intercambiadora de Sodio-Potasio/metabolismoAsunto(s)
Lipoproteínas/sangre , Fosfatidilcolinas/sangre , Triglicéridos/sangre , Animales , Apolipoproteínas/sangre , Colesterol/sangre , Ésteres del Colesterol/sangre , Lípidos/administración & dosificación , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Lipoproteínas VLDL/sangre , Masculino , Ratas , Esfingomielinas/sangre , Esteroles/sangreRESUMEN
In order to characterize the protein composition of rat bile, the bile duct was cannulated in 250 g male Wistar rats and biliary proteins were examined over 48 h. Total protein secretion was monitored by the Cu2+--Folin differential test while individual proteins were characterized by sodium dodecyl sulfate (SDS) and non-SDS polyacrylamide gel electrophoresis. The relative contribution of various proteins was evaluated by densitometric scanning of the stained gels. It was observed that both total biliary protein secretion and the protein polypeptide profiles remained constant throughout the 48h. This is in comparison with biliary bile-acid secretion which fluctuates markedly during this time period both in quantity and composition. It is concluded that biliary secretion is probably not related to the biliary secretion of bile acids.
Asunto(s)
Bilis/análisis , Proteínas/análisis , Animales , Ácidos y Sales Biliares/análisis , Electroforesis en Gel de Poliacrilamida , Masculino , Peso Molecular , RatasRESUMEN
The stereochemical course of in vivo hydrolysis of triacylglycerols by lipoprotein lipase was investigated by determining the structure of diacylglycerol intermediates in postheparin plasma of rats which had been fed [3H]glycerol-labeled Intralipid 2 h before an injection of heparin or had been given an injection of a mixture of [3H]glycerol-Intralipid and heparin. During the clearance of both the natural chylomicrons and the artificial emulsion, sn-2,3-diacylglycerols (60-80%) were found to be the dominant enantiomers. Similar results were obtained when the contribution of the hepatic lipase was altered, either by tying off the mesentery artery and portal vein before injection of heparin, or by injection of heparin directly into the portal vein. These findings are consistent with a preferential release of the acyl group from the sn-1 position of the triacylglycerol molecule as demonstrated previously in vitro. A preferential orientation of the substrate in the enzyme-substrate complex or at the oil-water interface is discussed as a possible basis for these effects.
Asunto(s)
Diglicéridos/sangre , Glicéridos/sangre , Animales , Heparina/farmacología , Isomerismo , Lipoproteína Lipasa/metabolismo , Hígado/enzimología , Fosfolipasas/metabolismo , Ratas , Especificidad por Sustrato , Trioleína/metabolismoAsunto(s)
Colesterol/análogos & derivados , Colesterol/biosíntesis , Hígado/metabolismo , Sitoesteroles/farmacología , Animales , Colesterol/farmacología , Hidroxicolesteroles/farmacología , Masculino , Plantas , Ratas , Sitoesteroles/metabolismo , Esteroles/metabolismo , Relación Estructura-ActividadRESUMEN
The bile acid pool was found to be ca. 50 mumoles/100 g body wt in male and female rats maintained on standard laboratory chow and ca. 30 mumoles/100 g body wt in those maintained on a standard semisynthetic diet. The distribution of bile acids within the pool was similar in plasma, liver, and intestinal tract, except for a higher concentration of deoxycholic acid in the intestinal tract. Sex differences in bile acid composition were found to be influenced by the dietary regimen of the animals.