title: Estrogen-induced cholestasis results in a dramatic increase of b-series gangliosides in the rat liver.
abstract: Hepatic ganglioside composition was investigated in normal and cholestatic Wistar rats. Cholestasis was induced by 17alpha-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.
authors.affiliation: Institute of Clinical Biochemistry and Laboratory Diagnostics, Charles University of Prague, 12808, Czech Republic.
authors.forename: Filip
authors.initials: F
authors.lastname: Majer
authors.forename: Ladislav
authors.initials: L
authors.lastname: Trnka
authors.forename: Libor
authors.initials: L
authors.lastname: Vítek
authors.forename: Marie
authors.initials: M
authors.lastname: Jirkovská
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Marecek
authors.forename: Frantisek
authors.initials: F
authors.lastname: Smíd
mesh_terms: D000818:Animals; D002779:Cholestasis / Q000139:chemically induced*; D002855:Chromatography, Thin Layer; D004997:Ethinyl Estradiol / Q000633:toxicity*; D005260:Female; D005732:Gangliosides / Q000096:biosynthesis / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005732:Gangliosides; D004997:Ethinyl Estradiol