SPHK1 and Hepatic failure: Indeed, in LPS/D-galactosamine (D-Gal)-induced liver failure, S1P levels were elevated, whilst the expression of SphK1, S1PR1, and S1PR3 was upregulated in the liver, and the levels of serum markers of liver failure, AST and ALT, and the serum cytokines TNF-α, IL-1, and IL-6 were increased (25).