TEC alleviated ANIT-induced and DDC-induced experimental
intrahepatic cholestasis
A previous study reported that ANIT and DDC treatment could cause
intestinal permeability, leading to the translocation of bacteria or
their products (LPS) from the leaky intestine into the
liver[14].
Additionally, whilst murine experimental models may not fully represent
human disease, ANIT and feeding with 0.1% DDC are well-accepted models
of sclerosing cholangitis relevant to
PSC[27,
28]. Thus, the hepatoprotective effect
of TEC was further confirmed in an experimental model of ANIT-induced
and DDC-induced CLD.
The ANIT-induced mouse model exhibits increased cholestasis-serum
markers and multiple large areas of necrosis, which can be significantly
relieved by TEC treatment (Figure 1A and 1B). In line with these
results, TEC inhibited ANIT-induced apoptotic cell death, as seen by
fewer positive areas on TUNEL staining and reduced caspase-3 activity
after TEC intervention (Figure 1C and 1D). Additionally, TEC alleviated
ANIT-induced inflammation as shown by a significant decrease in the
recruitment of macrophages in the liver (Figure 1E and 1F). Consistent
with this, our results showed that ANIT treatment significantly
increased the content of IL-1β in mouse serum (Figure 1G) and the mRNA
level of inflammatory factors in the liver (Figure 1H). As expected, TEC
intervention reduced the serum level of IL-1β and the expression of
hepatic inflammatory factors.