Tetrahydroxylated bile acids improve cholestatic liver and bile duct injury in the Mdr2^-/- mouse model of sclerosing cholangitis via immunomodulatory effects.

ABSTRACT: Bile salt export pump (Bsep) (Abcb11)^-/- mice are protected from acquired cholestatic injury due to metabolic preconditioning with a hydrophilic bile acid (BA) pool with formation of tetrahydroxylated bile acids (THBAs). We aimed to explore whether loss of Bsep and subsequent elevation of THBA levels may have immunomodulatory effects, thus improving liver injury in the multidrug resistance protein 2 (Mdr2) (Abcb4)^-/- mouse. Cholestatic liver injury in Mdr2^-/- Bsep^-/- double knockout (DKO), Mdr2^-/- , Bsep^-/- , and wild-type mice was studied for comparison. Mdr2^-/- mice were treated with a THBA (3α,6α,7α,12α-Tetrahydroxycholanoic acid). RNA/protein expression of inflammatory/fibrotic markers were investigated. Serum

SUBMITTER: Fuchs CD 

PROVIDER: S-EPMC9426398 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature