Inhibition of JNK signalling mediates PPARα-dependent protection against intrahepatic cholestasis by fenofibrate.

ABSTRACT:

Background and purpose

Fenofibrate, a PPARα agonist, is the most widely prescribed drug for treating hyperlipidaemia. Although fibrate drugs are reported to be beneficial for cholestasis, their underlying mechanism has not been determined.

Experimental approach

Wild-type mice and Pparα-null mice were pretreated orally with fenofibrate for 3 days, following which α-naphthylisothiocyanate (ANIT) was administered to induce cholestasis. The PPARα agonist WY14643 and JNK inhibitor SP600125 were used to determine the role of PPARα and the JNK pathway, respectively, in cholestatic liver injury. The same fenofibrate regimen was applied to investigate its beneficial effects on sclerosing cholangitis in a DDC-induced cholestatic model.

Key results

Fenofibrate, 25 mg·kg^-1</

SUBMITTER: Dai M 

PROVIDER: S-EPMC5573431 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature