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Warfarin‐induced vitamin K deficiency is associated with alterations in sphingolipid status in rats
Author(s) -
Ferland Guylaine,
Tamadonnejad Sahar,
Ouliass Bouchra
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.635.12
Subject(s) - sphingolipid , sphingomyelin , ceramide , medicine , endocrinology , chemistry , vitamin k deficiency , vitamin , cholesterol , biochemistry , apoptosis
Vitamin K (VK) is involved in sphingolipid metabolism and menaquinone‐4 (MK‐4), the main K vitamer in brain, is strongly correlated to cerebral sulfatides, sphingomyelin and gangliosides. Warfarin (W), a widely used oral anticoagulant, acts by blocking the VK cycle. In a previous report, we observed W‐induced VK deficiency (model of Price et al. 1982) to result in cognitive deficits, an observation associated with a drastic decrease in brain MK‐4. Here we report that in these rats, W‐tx is associated with an alteration in sphingolipid status. Male Wistar rats were treated with 15 mg W/kg/d (in drinking water) and subcutaneous VK (85 mg/kg), 3X/wk, for 10 wks; control rats were treated with normal water and injected with saline. Sphingolipids (gangliosides, ceramides, cerebrosides, sphingomyelin and sulfatides) were determined by solid phase chomatography and the ganglioside subtypes were further assessed by HPTLC. Compared to the control condition, W‐tx altered ceramides, sphingomyelin, sulfatides and gangliosides in specific brain regions (p<0.05) and resulted in a loss of correlation between sphingolipids and brain MK‐4. W‐tx also resulted in significant changes in gangliosides GD1a and GT1b in key brain regions (p<0.05). In conclusion, W‐induced VK deficiency alters sphingolipid status in brain, a finding that could contribute to the detrimental effects of W on cognition. (Funded by CIHR.)