Estrogen-induced cholestasis results in a dramatic increase of b-series gangliosides in the rat liver

Hepatic ganglioside composition was investigated in normal and cholestatic Wistar rats. Cholestasis was induced by 17α‐ethinylestradiol (EE; 5 mg/kg body weight s.c. for 18 days). As compared with controls, the EE administration resulted in severe cholestasis, as indicated by biochemical as well as...

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Published in:Biomedical chromatography 2007-05, Vol.21 (5), p.446-450
Main Authors: Majer, Filip, Trnka, Ladislav, Vítek, Libor, Jirkovská, Marie, Mareček, Zdeněk, Šmíd, František
Format: Article
Language:English
Subjects:
Animals
b-pathway of ganglioside biosynthesis
cholestasis
Cholestasis - chemically induced
Chromatography, Thin Layer
Ethinyl Estradiol - toxicity
ethinylestradiol
Female
gangliosides
Gangliosides - biosynthesis
Gangliosides - metabolism
Liver - drug effects
Liver - metabolism
rat liver
Rats
Rats, Wistar
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Summary:Hepatic ganglioside composition was investigated in normal and cholestatic Wistar rats. Cholestasis was induced by 17α‐ethinylestradiol (EE; 5 mg/kg body weight s.c. for 18 days). As compared with controls, the EE administration resulted in severe cholestasis, as indicated by biochemical as well as morphological signs. Gangliosides isolated from the liver tissue were separated by TLC, with resorcinol‐HCl detection and densitometric evaluation. As compared with controls, the total hepatic lipid sialic acid content in cholestatic rats was increased almost 2‐fold (44.3 ± 15.2 vs 79.1 ± 9.0 nmol/g wet weight of liver tissue, p < 0.01). This increase was primarily due to the increase of ganglioside GD1a (3.6 ± 1.0 vs 11.8 ± 3.0 nmol/g wet weight of liver tissue, p = 0.001), as well as to the enormous up‐regulation of b‐series gangliosides GD3 (0.08 ± 0.03 vs 2.0 ± 1.2 nmol/g wet weight of liver tissue, p = 0.002), GD1b (0.1 ± 0.06 vs 5.4 ± 1.6 nmol/g wet weight of liver tissue, p = 0.002) and GT1b (0.06 ± 0.03 vs 6.4 ± 2.6 nmol/g wet weight of liver tissue, p = 0.002). As the majority of gangliosides are concentrated in cell membranes, our findings suggest that dramatic increase of b‐series gangliosides might contribute to the protection of hepatocytes against the deleterious effects of cholestasis. Copyright © 2007 John Wiley & Sons, Ltd.
ISSN:0269-3879
1099-0801
DOI:10.1002/bmc.743