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Alina Pyka - One of the best experts on this subject based on the ideXlab platform.
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Lipophilicity of Selected Bile Acids as Determined by TLC. III. Investigations on RP2 Stationary Phase
Journal of Liquid Chromatography & Related Technologies, 2020Co-Authors: Alina Pyka, Małgorzata DołowyAbstract:Abstract The following bile Acids: cholic Acid (C), glycocholic Acid (GC), Glycodeoxycholic Acid (GDC), chenodeoxycholic (CDC), deoxycholic Acid (DC), lithocholic Acid (LC), and glycolithocholic Acid (GLC) were investigated with the use of reversed phase thin‐layer chromatography on RP2 plates (E. Merck, # 1.13726) using methanol‐water, organic mixture (acetonitrile‐methanol 50:50, v/v)‐water, acetone‐water, dioxane‐water in different volume compositions as mobile phases. The chromatographic parameters of lipophilicity (RMW and ϕ0) of studied bile Acids were determined. Lipophilic parameters (RMW and ϕ0) were compared, both with measured partition coefficients (logPexp) and calculated ones (AlogPS, IAlogP, logPKOWIN, xlogP, clogP, logPRekker). The most significant correlation was found between RMW and ϕ0 lipophilic parameters and logPKOWIN values. IAlogP correlates with the a/m lipophilic parameters slightly more poorly than logPKOWIN does. The values of RMW and ϕ0 lipophilic parameters obtained on both, ...
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Separation of Selected Bile Acids by TLC. VI. Separation on Cyano‐ and Diol‐Modified Silica Layers
Journal of Liquid Chromatography & Related Technologies, 2020Co-Authors: Alina Pyka, Małgorzata DołowyAbstract:Abstract Seven selected bile Acids: cholic Acid (C), glycocholic Acid (GC), glycolithocholic Acid (GLC), deoxycholic Acid (DC), chenodeoxycholic Acid (CDC), Glycodeoxycholic Acid (GDC), and lithocholic Acid (LC) were separated on silica gel modified by cyano and diol groups, with the use of a mobile phase: n‐hexane–ethyl acetate–acetic Acid in different volume compositions, at 18°C. The estimation of separation was carried out on the basis of the separation factors values: ΔRF and RS. Almost all bile Acids, except for CDC/DC, were completely separated on cyano‐modified silica plates when a mobile phase n‐hexane–ethyl acetate–acetic Acid in the volume composition 49:49:2 was used; whereas, the optimal separation for all examined bile Acids was obtained on diol plates, using a mobile phase n‐hexane–ethyl acetate–acetic Acid in the volume composition 42:42:16.
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Separation of Selected Bile Acids by TLC. VII. Separation by Reversed Partition HPTLC
Journal of Liquid Chromatography & Related Technologies, 2020Co-Authors: Alina Pyka, Małgorzata DołowyAbstract:Abstract Selected bile Acids: cholic Acid (C), glycocholic Acid (GC), Glycodeoxycholic Acid (GDC), chenodeoxycholic Acid (CDC), deoxycholic Acid (DC), lithocholic Acid (LC), and glycolithocholic Acid (GLC) were investigated with the use of reversed phase high performance thin‐layer chromatography on RP18W (E. Merck, #1.14296), RP18 (E. Merck, #1.05914), RP2 (E. Merck, #1.13726), and CNF254 (E. Merck, #1.12571) plates using methanol–water, organic mixture (acetonitrile–methanol 50:50, v/v)–water, acetone–water, dioxane–water, and acetonitrile–phosphate buffer (pH 4.60) as mobile phases, in different volume compositions. The obtained separations were carried out on the basis of separation factors values ΔRF and RS. None of the applied chromatographic conditions enabled completion of the separation of all examined bile Acids. Five neighboring bile Acids, i.e., LC/DC, CDC/GLC, GLC/C, C/GDC, GDC/GC, were separated only when CNF254 plates and the mobile phase acetone–water, 50:50; v/v were used. The biggest pro...
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Use of Structural Descriptors to QSRR Analysis of Selected Bile Acids Separated by NP-TLC
Journal of Liquid Chromatography & Related Technologies, 2009Co-Authors: Alina PykaAbstract:Abstract The selected bile Acids such as: cholic Acid (C), glycocholic Acid (GC), glycolithocholic Acid (GLC), deoxycholic Acid (DC), chenodeoxycholic Acid (CDC), Glycodeoxycholic Acid (GDC), lithocholic Acid (LC), were separated by using normal phase thin-layer chromatography (NP-TLC) on glass plates precoated with silica gel 60 with concentrating zone (E. Merck, #1.11845) and n-hexane-ethyl acetate–methanol-acetic Acid in volume composition 20:20:5:2 as the mobile phase. The selected topological indexes based on connectivity (Mν, 0χν, 1χν, 2χν, and ), on distance matrix (W, A, 0B, 1B, and C), and selected electrotopological states (SdO(Acid), SsOH(Acid), SsOH(aliph), SdO(amide), and SsNH) were calculated for investigated bile Acids. The most accurate prediction of the RM values of the investigated bile Acids was achieved by using a monoparametric equation employing the topological index Mν.
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Separation of Selected Bile Acids by TLC. III. Separation on Various Stationary Phases
Journal of Liquid Chromatography & Related Technologies, 2009Co-Authors: Alina Pyka, Małgorzata DołowyAbstract:Abstract The aim of our study was to determine the optimum conditions of the separation of selected bile Acids, such as cholic Acid (C), glycocholic Acid (GC), glycolithocholic Acid (GLC), deoxycholic Acid (DC), chenodeoxycholic Acid (CDC), Glycodeoxycholic Acid (GDC), and lithocholic Acid (LC) using thin‐layer chromatography on aluminum plates which are precoated with silica gel 60 (E. Merck, #1.05553), silica gel 60F 254 (E. Merck, #1.05554), a mixture of silica gel 60 and Kieselguhr F 254 (E. Merck, #1.05567), as well as on glass plates which are precoated with silica gel 60F 254 (E. Merck, #1.05715) and on glass plates precoated with silica gel 60F 254 with a concentrating zone (E. Merck, #1.11798) using n‐hexane–ethyl acetate–acetic Acid in various volume compositions as mobile phases. The retardation factor (R f), and separation factors ΔR f and R S of each pair of examined bile Acids were obtained. All bile Acids have been successfully separated only on glass and aluminum plates precoated with sili...
Małgorzata Dołowy - One of the best experts on this subject based on the ideXlab platform.
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Lipophilicity of Selected Bile Acids as Determined by TLC. III. Investigations on RP2 Stationary Phase
Journal of Liquid Chromatography & Related Technologies, 2020Co-Authors: Alina Pyka, Małgorzata DołowyAbstract:Abstract The following bile Acids: cholic Acid (C), glycocholic Acid (GC), Glycodeoxycholic Acid (GDC), chenodeoxycholic (CDC), deoxycholic Acid (DC), lithocholic Acid (LC), and glycolithocholic Acid (GLC) were investigated with the use of reversed phase thin‐layer chromatography on RP2 plates (E. Merck, # 1.13726) using methanol‐water, organic mixture (acetonitrile‐methanol 50:50, v/v)‐water, acetone‐water, dioxane‐water in different volume compositions as mobile phases. The chromatographic parameters of lipophilicity (RMW and ϕ0) of studied bile Acids were determined. Lipophilic parameters (RMW and ϕ0) were compared, both with measured partition coefficients (logPexp) and calculated ones (AlogPS, IAlogP, logPKOWIN, xlogP, clogP, logPRekker). The most significant correlation was found between RMW and ϕ0 lipophilic parameters and logPKOWIN values. IAlogP correlates with the a/m lipophilic parameters slightly more poorly than logPKOWIN does. The values of RMW and ϕ0 lipophilic parameters obtained on both, ...
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Separation of Selected Bile Acids by TLC. VI. Separation on Cyano‐ and Diol‐Modified Silica Layers
Journal of Liquid Chromatography & Related Technologies, 2020Co-Authors: Alina Pyka, Małgorzata DołowyAbstract:Abstract Seven selected bile Acids: cholic Acid (C), glycocholic Acid (GC), glycolithocholic Acid (GLC), deoxycholic Acid (DC), chenodeoxycholic Acid (CDC), Glycodeoxycholic Acid (GDC), and lithocholic Acid (LC) were separated on silica gel modified by cyano and diol groups, with the use of a mobile phase: n‐hexane–ethyl acetate–acetic Acid in different volume compositions, at 18°C. The estimation of separation was carried out on the basis of the separation factors values: ΔRF and RS. Almost all bile Acids, except for CDC/DC, were completely separated on cyano‐modified silica plates when a mobile phase n‐hexane–ethyl acetate–acetic Acid in the volume composition 49:49:2 was used; whereas, the optimal separation for all examined bile Acids was obtained on diol plates, using a mobile phase n‐hexane–ethyl acetate–acetic Acid in the volume composition 42:42:16.
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Separation of Selected Bile Acids by TLC. VII. Separation by Reversed Partition HPTLC
Journal of Liquid Chromatography & Related Technologies, 2020Co-Authors: Alina Pyka, Małgorzata DołowyAbstract:Abstract Selected bile Acids: cholic Acid (C), glycocholic Acid (GC), Glycodeoxycholic Acid (GDC), chenodeoxycholic Acid (CDC), deoxycholic Acid (DC), lithocholic Acid (LC), and glycolithocholic Acid (GLC) were investigated with the use of reversed phase high performance thin‐layer chromatography on RP18W (E. Merck, #1.14296), RP18 (E. Merck, #1.05914), RP2 (E. Merck, #1.13726), and CNF254 (E. Merck, #1.12571) plates using methanol–water, organic mixture (acetonitrile–methanol 50:50, v/v)–water, acetone–water, dioxane–water, and acetonitrile–phosphate buffer (pH 4.60) as mobile phases, in different volume compositions. The obtained separations were carried out on the basis of separation factors values ΔRF and RS. None of the applied chromatographic conditions enabled completion of the separation of all examined bile Acids. Five neighboring bile Acids, i.e., LC/DC, CDC/GLC, GLC/C, C/GDC, GDC/GC, were separated only when CNF254 plates and the mobile phase acetone–water, 50:50; v/v were used. The biggest pro...
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Separation of Selected Bile Acids by TLC. III. Separation on Various Stationary Phases
Journal of Liquid Chromatography & Related Technologies, 2009Co-Authors: Alina Pyka, Małgorzata DołowyAbstract:Abstract The aim of our study was to determine the optimum conditions of the separation of selected bile Acids, such as cholic Acid (C), glycocholic Acid (GC), glycolithocholic Acid (GLC), deoxycholic Acid (DC), chenodeoxycholic Acid (CDC), Glycodeoxycholic Acid (GDC), and lithocholic Acid (LC) using thin‐layer chromatography on aluminum plates which are precoated with silica gel 60 (E. Merck, #1.05553), silica gel 60F 254 (E. Merck, #1.05554), a mixture of silica gel 60 and Kieselguhr F 254 (E. Merck, #1.05567), as well as on glass plates which are precoated with silica gel 60F 254 (E. Merck, #1.05715) and on glass plates precoated with silica gel 60F 254 with a concentrating zone (E. Merck, #1.11798) using n‐hexane–ethyl acetate–acetic Acid in various volume compositions as mobile phases. The retardation factor (R f), and separation factors ΔR f and R S of each pair of examined bile Acids were obtained. All bile Acids have been successfully separated only on glass and aluminum plates precoated with sili...
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Separation of Selected Bile Acids by TLC. IX. Separation on Silica Gel 60 and on Silica Gel 60F254 Aluminum Plates Impregnated with Cu(II), Ni(II), Fe(II), and Mn(II) Cations
Journal of Liquid Chromatography & Related Technologies, 2007Co-Authors: Małgorzata DołowyAbstract:Abstract Seven selected bile Acids: cholic Acid (C), glycocholic Acid (GC), glycolithocholic Acid (GLC), deoxycholic Acid (DC), chenodeoxycholic Acid (CDC), Glycodeoxycholic Acid (GDC), and lithocholic Acid (LC) were separated using adsorption TLC on aluminum plates precoated with silica gel 60 and on aluminum plates precoated with silica gel 60F254. The plates were impregnated with 1%, 2.5%, and 5% aqueous solutions of the following salts: CuSO4, MnSO4, NiSO4, and FeSO4. The mixtures of n–hexane–ethyl–acetate–acetic Acid in the volume compositions: 22:20:5 and 25:20:2 (v/v/v) for both aluminum plates, 22:22:5 (v/v/v) only for #1.05554 plates and 25:20:5 (v/v/v) for #1.05553 plates were used as mobile phases. These mobile phases were not effective for the separation of bile Acids on non impregnated silica gel 60 and silica 60F254 aluminum plates at 18°C. The plates impregnated with the salts whose application resulted in ΔRF≥0.05 and RS>1 for all neighboring pairs of examined bile Acids were considered th...
Lien B Nguyen - One of the best experts on this subject based on the ideXlab platform.
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Increasing hepatic cholesterol 7α‐hydroxylase reduces plasma cholesterol concentrations in normocholesterolemic and hypercholesterolemic rabbits
Hepatology, 1996Co-Authors: Guorong Xu, Lien B Nguyen, Gene C Ness, Gerald Salen, Sarah Shefer, G S Tint, Thomas S. Parker, J. Roberts, Ashok K. Batta, Thomas S ChenAbstract:Abstract The effect of bile Acid depletion and replacement with Glycodeoxycholic Acid on plasma cholesterol concentrations, hepatic low-density lipoprotein (LDL) receptor binding and messenger RNA (mRNA) levels, and hepatic activities and mRNA levels for 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and cholesterol 7alpha-hydroxylase was investigated in 19 New Zealand white (NZW) and 15 Watanabe heritable hyperlipidemic (WHHL) rabbits. Bile Acid depletion was produced by external bile drainage for 5 days, which maximized cholic Acid synthesis. Replacement was achieved by infusing Glycodeoxycholic Acid intraduodenally for 24 hours so that the hepatic bile Acid flux reached prefistula levels. Plasma and liver cholesterol concentrations were 13 times and 50% greater, respectively, hepatic LDL receptor-mediated binding was 26% less, and cholesterol 7alpha-hydroxylase activity and mRNA levels were 62% and 86% less in WHHL than NZW rabbits. After bile drainage, plasma cholesterol concentrations decreased 29% in NZW rabbits and 40% in WHHL rabbits and were associated with a 2.1-fold increase in hepatic LDL receptor-mediated binding in the NZW rabbits, but there was no change in the WHHL rabbits. Cholesterol 7alpha- hydroxylase activity and mRNA levels increased three and four times in NZW and WHHL rabbits, respectively, although liver cholesterol levels remained unchanged. Replacement with exogenous Glycodeoxycholic Acid increased plasma cholesterol concentrations 1.7 times in NZW rabbits and decreased enhanced cholesterol 7alpha-hydroxylase activity 54%, mRNA levels 86%, cholic Acid synthesis 38%, and hepatic LDL receptor- mediated binding 57% in NZW rabbits. Bile Acid depletion stimulated cholic Acid synthesis by up-regulating cholesterol 7alpha-hydroxylase to use cholesterol and reduce plasma concentrations substantially in both NZW and WHHL rabbits, although LDL receptors did not function in WHHL rabbits. Glycodeoxycholic Acid replacement inhibited elevated cholesterol 7alpha-hydroxylase, cholic Acid synthesis, and hepatic LDL receptor binding to reestablish baseline plasma cholesterol levels in NZW rabbits. Hypercholesterolemia in WHHL rabbits was related to the combination of dysfunctional LDL receptors and inhibited cholesterol 7alpha-hydroxylase. Plasma cholesterol concentrations were reduced significantly when cholesterol 7alpha-hydroxylase was stimulated even in the absence of LDL receptor function. (Hepatology 1996 Oct;24(4):882-7)
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different feedback regulation of hepatic cholesterol and bile Acid synthesis by Glycodeoxycholic Acid in rabbits
Gastroenterology, 1993Co-Authors: Guorong Xu, G Salen, A K Batta, S Shefer, Lien B Nguyen, Gene C Ness, Zhihong Zhao, Thomas S Chen, Wendell Niemann, Stephen G TintAbstract:Abstract Background: To explore the sexual difference in the feedback regulation of hepatic bile Acid synthesis, Glycodeoxycholic Acid (GDCA) was administered to 15 male and 14 female rabbits. Methods: After bile diversion, GDCA equivalent to the hepatic bile Acid influx was infused intraduodenally. Biliary cholic Acid output represented bile Acid synthesis. Hepatic 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase and cholesterol 7α-hydroxylase activities and steady state messenger RNA (mRNA) levels were determined. Results: GDCA inhibited bile Acid synthesis less in female than in male rabbits. Hepatic HMG-CoA reductase activity decreased 39% in males, but increased 48% in females. Hepatic cholesterol 7α-hydroxylase activity decreased similarly in males and females, and mRNA levels decreased 86% in males but were unchanged in females. Conclusions: (1) Total bile diversion stimulated both hepatic cholesterol and bile Acid synthesis by activating the rate-controlling enzymes and increasing mRNA levels. (2) GDCA decreased mRNA levels of HMG-CoA reductase and cholesterol 7α-hydroxylase in males, but mRNA levels did not decrease in females. (3) Bile Acid synthesis was sustained in females because continued biosynthesis of cholesterol provided a substrate for cholesterol 7α-hydroxylase and stimulus for enzyme formation.
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glycocholic Acid and Glycodeoxycholic Acid but not glycoursocholic Acid inhibit bile Acid synthesis in the rabbit
Gastroenterology, 1992Co-Authors: Guorong Xu, G Salen, A K Batta, S Shefer, Lien B NguyenAbstract:Abstract Feedback regulation of derepressed hepatic bile Acid biosynthesis was studied individually with glycocholic, Glycodeoxycholic, and glycoursocholic Acids by infusion into bile Acid-depleted rabbits. Construction of a bile fistula drained the endogenous bile Acid pool (90% Glycodeoxycholic Acid, 10% glycocholic Acid) within 24 hours and elicited maximal bile Acid synthesis after about 72 hours, at which time glycocholic Acid became the only biliary bile Acid (>98%). Replacement of the bile Acid pool with glycocholic Acid or Glycodeoxycholic Acid at a rate equivalent to the hepatic endogenous bile Acid flux inhibited endogenous biosynthesis by 40%. In contrast, glycoursocholic Acid, the 7β-hydroxy epimer of glycocholic Acid, failed to suppress synthesis. Hepatic bile Acid depletion increased hydroxymethyglutary coenzyme A (HMG-CoA) reductase activity fourfold and cholesterol 7α-hydroxylase activity threefold, which were reduced 48% and 51%, respectively, from their maximum levels during replacement with glycocholic Acid. Glycodeoxycholic Acid infusion depressed cholesterol 7α-hydroxylase activity by 59% without reducing HMG-CoA reductase activity significantly. There was no significant change in the activity of either enzyme during glycoursocholic Acid infusion. Biliary cholesterol and cholestanol secretion declined 13% and 53%, respectively, during glycocholic Acid infusion, were not affected by Glycodeoxycholic Acid infusion, but increased 19% and 43%, respectively, during glycoursocholic Acid infusion. These results show that in rabbits the feedback regulation of hepatic bile Acid synthesis depends on the hepatic flux of the normally present endogenous bile Acids glycocholic Acid and Glycodeoxycholic Acid but does not respond to the 7β-hydroxy glycoursocholic Acid. Glycocholic Acid inhibits both HMG-CoA reductase and cholesterol 7α-hydroxylase while Glycodeoxycholic Acid affects primarily cholesterol 7α-hydroxylase. Thus, the regulation of bile Acid synthesis may be mediated by both the availability of cholesterol substrate and the activity of the rate-determining enzyme for bile Acid synthesis.
Guorong Xu - One of the best experts on this subject based on the ideXlab platform.
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Increasing hepatic cholesterol 7α‐hydroxylase reduces plasma cholesterol concentrations in normocholesterolemic and hypercholesterolemic rabbits
Hepatology, 1996Co-Authors: Guorong Xu, Lien B Nguyen, Gene C Ness, Gerald Salen, Sarah Shefer, G S Tint, Thomas S. Parker, J. Roberts, Ashok K. Batta, Thomas S ChenAbstract:Abstract The effect of bile Acid depletion and replacement with Glycodeoxycholic Acid on plasma cholesterol concentrations, hepatic low-density lipoprotein (LDL) receptor binding and messenger RNA (mRNA) levels, and hepatic activities and mRNA levels for 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and cholesterol 7alpha-hydroxylase was investigated in 19 New Zealand white (NZW) and 15 Watanabe heritable hyperlipidemic (WHHL) rabbits. Bile Acid depletion was produced by external bile drainage for 5 days, which maximized cholic Acid synthesis. Replacement was achieved by infusing Glycodeoxycholic Acid intraduodenally for 24 hours so that the hepatic bile Acid flux reached prefistula levels. Plasma and liver cholesterol concentrations were 13 times and 50% greater, respectively, hepatic LDL receptor-mediated binding was 26% less, and cholesterol 7alpha-hydroxylase activity and mRNA levels were 62% and 86% less in WHHL than NZW rabbits. After bile drainage, plasma cholesterol concentrations decreased 29% in NZW rabbits and 40% in WHHL rabbits and were associated with a 2.1-fold increase in hepatic LDL receptor-mediated binding in the NZW rabbits, but there was no change in the WHHL rabbits. Cholesterol 7alpha- hydroxylase activity and mRNA levels increased three and four times in NZW and WHHL rabbits, respectively, although liver cholesterol levels remained unchanged. Replacement with exogenous Glycodeoxycholic Acid increased plasma cholesterol concentrations 1.7 times in NZW rabbits and decreased enhanced cholesterol 7alpha-hydroxylase activity 54%, mRNA levels 86%, cholic Acid synthesis 38%, and hepatic LDL receptor- mediated binding 57% in NZW rabbits. Bile Acid depletion stimulated cholic Acid synthesis by up-regulating cholesterol 7alpha-hydroxylase to use cholesterol and reduce plasma concentrations substantially in both NZW and WHHL rabbits, although LDL receptors did not function in WHHL rabbits. Glycodeoxycholic Acid replacement inhibited elevated cholesterol 7alpha-hydroxylase, cholic Acid synthesis, and hepatic LDL receptor binding to reestablish baseline plasma cholesterol levels in NZW rabbits. Hypercholesterolemia in WHHL rabbits was related to the combination of dysfunctional LDL receptors and inhibited cholesterol 7alpha-hydroxylase. Plasma cholesterol concentrations were reduced significantly when cholesterol 7alpha-hydroxylase was stimulated even in the absence of LDL receptor function. (Hepatology 1996 Oct;24(4):882-7)
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different feedback regulation of hepatic cholesterol and bile Acid synthesis by Glycodeoxycholic Acid in rabbits
Gastroenterology, 1993Co-Authors: Guorong Xu, G Salen, A K Batta, S Shefer, Lien B Nguyen, Gene C Ness, Zhihong Zhao, Thomas S Chen, Wendell Niemann, Stephen G TintAbstract:Abstract Background: To explore the sexual difference in the feedback regulation of hepatic bile Acid synthesis, Glycodeoxycholic Acid (GDCA) was administered to 15 male and 14 female rabbits. Methods: After bile diversion, GDCA equivalent to the hepatic bile Acid influx was infused intraduodenally. Biliary cholic Acid output represented bile Acid synthesis. Hepatic 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase and cholesterol 7α-hydroxylase activities and steady state messenger RNA (mRNA) levels were determined. Results: GDCA inhibited bile Acid synthesis less in female than in male rabbits. Hepatic HMG-CoA reductase activity decreased 39% in males, but increased 48% in females. Hepatic cholesterol 7α-hydroxylase activity decreased similarly in males and females, and mRNA levels decreased 86% in males but were unchanged in females. Conclusions: (1) Total bile diversion stimulated both hepatic cholesterol and bile Acid synthesis by activating the rate-controlling enzymes and increasing mRNA levels. (2) GDCA decreased mRNA levels of HMG-CoA reductase and cholesterol 7α-hydroxylase in males, but mRNA levels did not decrease in females. (3) Bile Acid synthesis was sustained in females because continued biosynthesis of cholesterol provided a substrate for cholesterol 7α-hydroxylase and stimulus for enzyme formation.
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glycocholic Acid and Glycodeoxycholic Acid but not glycoursocholic Acid inhibit bile Acid synthesis in the rabbit
Gastroenterology, 1992Co-Authors: Guorong Xu, G Salen, A K Batta, S Shefer, Lien B NguyenAbstract:Abstract Feedback regulation of derepressed hepatic bile Acid biosynthesis was studied individually with glycocholic, Glycodeoxycholic, and glycoursocholic Acids by infusion into bile Acid-depleted rabbits. Construction of a bile fistula drained the endogenous bile Acid pool (90% Glycodeoxycholic Acid, 10% glycocholic Acid) within 24 hours and elicited maximal bile Acid synthesis after about 72 hours, at which time glycocholic Acid became the only biliary bile Acid (>98%). Replacement of the bile Acid pool with glycocholic Acid or Glycodeoxycholic Acid at a rate equivalent to the hepatic endogenous bile Acid flux inhibited endogenous biosynthesis by 40%. In contrast, glycoursocholic Acid, the 7β-hydroxy epimer of glycocholic Acid, failed to suppress synthesis. Hepatic bile Acid depletion increased hydroxymethyglutary coenzyme A (HMG-CoA) reductase activity fourfold and cholesterol 7α-hydroxylase activity threefold, which were reduced 48% and 51%, respectively, from their maximum levels during replacement with glycocholic Acid. Glycodeoxycholic Acid infusion depressed cholesterol 7α-hydroxylase activity by 59% without reducing HMG-CoA reductase activity significantly. There was no significant change in the activity of either enzyme during glycoursocholic Acid infusion. Biliary cholesterol and cholestanol secretion declined 13% and 53%, respectively, during glycocholic Acid infusion, were not affected by Glycodeoxycholic Acid infusion, but increased 19% and 43%, respectively, during glycoursocholic Acid infusion. These results show that in rabbits the feedback regulation of hepatic bile Acid synthesis depends on the hepatic flux of the normally present endogenous bile Acids glycocholic Acid and Glycodeoxycholic Acid but does not respond to the 7β-hydroxy glycoursocholic Acid. Glycocholic Acid inhibits both HMG-CoA reductase and cholesterol 7α-hydroxylase while Glycodeoxycholic Acid affects primarily cholesterol 7α-hydroxylase. Thus, the regulation of bile Acid synthesis may be mediated by both the availability of cholesterol substrate and the activity of the rate-determining enzyme for bile Acid synthesis.
G Salen - One of the best experts on this subject based on the ideXlab platform.
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different feedback regulation of hepatic cholesterol and bile Acid synthesis by Glycodeoxycholic Acid in rabbits
Gastroenterology, 1993Co-Authors: Guorong Xu, G Salen, A K Batta, S Shefer, Lien B Nguyen, Gene C Ness, Zhihong Zhao, Thomas S Chen, Wendell Niemann, Stephen G TintAbstract:Abstract Background: To explore the sexual difference in the feedback regulation of hepatic bile Acid synthesis, Glycodeoxycholic Acid (GDCA) was administered to 15 male and 14 female rabbits. Methods: After bile diversion, GDCA equivalent to the hepatic bile Acid influx was infused intraduodenally. Biliary cholic Acid output represented bile Acid synthesis. Hepatic 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase and cholesterol 7α-hydroxylase activities and steady state messenger RNA (mRNA) levels were determined. Results: GDCA inhibited bile Acid synthesis less in female than in male rabbits. Hepatic HMG-CoA reductase activity decreased 39% in males, but increased 48% in females. Hepatic cholesterol 7α-hydroxylase activity decreased similarly in males and females, and mRNA levels decreased 86% in males but were unchanged in females. Conclusions: (1) Total bile diversion stimulated both hepatic cholesterol and bile Acid synthesis by activating the rate-controlling enzymes and increasing mRNA levels. (2) GDCA decreased mRNA levels of HMG-CoA reductase and cholesterol 7α-hydroxylase in males, but mRNA levels did not decrease in females. (3) Bile Acid synthesis was sustained in females because continued biosynthesis of cholesterol provided a substrate for cholesterol 7α-hydroxylase and stimulus for enzyme formation.
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glycocholic Acid and Glycodeoxycholic Acid but not glycoursocholic Acid inhibit bile Acid synthesis in the rabbit
Gastroenterology, 1992Co-Authors: Guorong Xu, G Salen, A K Batta, S Shefer, Lien B NguyenAbstract:Abstract Feedback regulation of derepressed hepatic bile Acid biosynthesis was studied individually with glycocholic, Glycodeoxycholic, and glycoursocholic Acids by infusion into bile Acid-depleted rabbits. Construction of a bile fistula drained the endogenous bile Acid pool (90% Glycodeoxycholic Acid, 10% glycocholic Acid) within 24 hours and elicited maximal bile Acid synthesis after about 72 hours, at which time glycocholic Acid became the only biliary bile Acid (>98%). Replacement of the bile Acid pool with glycocholic Acid or Glycodeoxycholic Acid at a rate equivalent to the hepatic endogenous bile Acid flux inhibited endogenous biosynthesis by 40%. In contrast, glycoursocholic Acid, the 7β-hydroxy epimer of glycocholic Acid, failed to suppress synthesis. Hepatic bile Acid depletion increased hydroxymethyglutary coenzyme A (HMG-CoA) reductase activity fourfold and cholesterol 7α-hydroxylase activity threefold, which were reduced 48% and 51%, respectively, from their maximum levels during replacement with glycocholic Acid. Glycodeoxycholic Acid infusion depressed cholesterol 7α-hydroxylase activity by 59% without reducing HMG-CoA reductase activity significantly. There was no significant change in the activity of either enzyme during glycoursocholic Acid infusion. Biliary cholesterol and cholestanol secretion declined 13% and 53%, respectively, during glycocholic Acid infusion, were not affected by Glycodeoxycholic Acid infusion, but increased 19% and 43%, respectively, during glycoursocholic Acid infusion. These results show that in rabbits the feedback regulation of hepatic bile Acid synthesis depends on the hepatic flux of the normally present endogenous bile Acids glycocholic Acid and Glycodeoxycholic Acid but does not respond to the 7β-hydroxy glycoursocholic Acid. Glycocholic Acid inhibits both HMG-CoA reductase and cholesterol 7α-hydroxylase while Glycodeoxycholic Acid affects primarily cholesterol 7α-hydroxylase. Thus, the regulation of bile Acid synthesis may be mediated by both the availability of cholesterol substrate and the activity of the rate-determining enzyme for bile Acid synthesis.