i(3)so3-galactosylceramide and Renal-Insufficiency--Chronic

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.

Topics: Animals; Cell Line, Tumor; Liver; Male; Mice; Mice, Inbred C57BL; Renal Insufficiency, Chronic; Sulfoglycosphingolipids

Oxidative stress (OS) is a strong risk factor for cardiovascular disease (CVD). The incidence of CVD is lower among kidney transplantation (KT) recipients than hemodialysis patients, and the reduction in OS may be one reason for this difference. Recently, serum sulfatides were recognized as a candidate inhibitory factor of CVD affected by OS. However, the long-term changes in OS and serum sulfatide levels in KT recipients are unknown.. We investigated the long-term changes in a serum OS marker, malondialdehyde (MDA), and the serum sulfatide levels in 17 KT recipients. Multiple regression analysis was used to analyze the factors correlated with serum sulfatide levels.. The high serum levels of MDA in the KT recipients decreased dramatically but were still high 1 year after KT surgery. MDA levels decreased further and reached near-normal levels more than 3 years after the surgery. Similarly, over the same 3 years, the low serum sulfatide levels increased to near-normal levels, reaching saturation. Multiple regression analysis showed that the most significant factors influencing serum sulfatide levels were MDA and total cholesterol content.. The current results show that over the long term, the internal improvement brought about by successful KT can normalize OS. Oxidative normalization was significantly correlated with the restoration of serum sulfatide levels, which were also influenced by lipoprotein metabolism. The amelioration of serum sulfatide levels might contribute to the low incidence of CVD in KT recipients.

Topics: Adult; Biomarkers; Cardiovascular Diseases; Cholesterol; Female; Humans; Incidence; Japan; Kidney; Kidney Transplantation; Longitudinal Studies; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Regression Analysis; Renal Insufficiency, Chronic; Risk Factors; Sulfoglycosphingolipids