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.