Serum
sulfatides are critical
glycosphingolipids that are present in
lipoproteins and exert
anticoagulant effects. A previous study reported decreased levels of serum
sulfatides in
hemodialysis patients and suggested an association with
cardiovascular disease. However, the mechanism of changes in serum
sulfatides in chronic kidney dysfunction has not been well investigated. The current study examined whether a
chronic kidney disease (CKD) state could decrease serum
sulfatide levels using 5/6
nephrectomy (5/6NCKD) mice, an established CKD murine model, and studied the mechanisms contributing to diminished
sulfatides. 5/6NCKD mice and
sham operation control mice were sacrificed at the 4th or 12th postoperative week (POW) for measurement of serum
sulfatide levels. Hepatic
sulfatide content, which is the origin of serum
sulfatides, and the expression of
sulfatide metabolic
enzymes in liver tissue were assessed as well. The 5/6NCKD mice developed CKD and showed increased serum
creatinine and
indoxyl sulfate. The serum levels and hepatic amounts of
sulfatides were significantly decreased in 5/6NCKD mice at both 4 and 12 POW, while the degradative
enzymes of
sulfatides arylsulfatase A and
galactosylceramidase were significantly increased. In a Hepa1-6 murine liver cell line,
indoxyl sulfate addition caused intracellular levels of
sulfatides to decrease and degradative
enzymes of
sulfatides to increase in a manner comparable to the changes in 5/6NCKD mice liver tissue. In conclusion, chronic kidney dysfunction causes degradation of
sulfatides in the liver to decrease serum
sulfatide levels. One explanation of these results is that
indoxyl sulfate, a uremic toxin, accelerates the degradation of
sulfatides in liver tissue.