posted on 2024-01-25, 04:03authored byChenglong Fei, Lei Liu, Hedong Qi, Yuyang Peng, Jingfen Han, Chunru Wang, Xue Li
Autoimmune hepatitis
(AIH) is a severe immune-mediated inflammatory
liver disease whose standard of care is immunosuppressive treatment
with inevitable undesired outcomes. Macrophage is acknowledged to
aggravate liver damage, providing a promising AIH therapeutic target.
Accordingly, in this study, a kind of curdlan-decorated fullerene
nanoparticle (Cur-F) is fabricated to alleviate immune-mediated hepatic
injury for treating AIH via reducing macrophage infiltration in a
concanavalin A (Con A)-induced AIH mouse model. After intravenous
administration, Cur-F primarily distributes in liver tissues, efficiently
eliminates the excessive reactive oxygen species, significantly attenuates
oxidative stress, and subsequently suppresses the nuclear factor kappa-B-gene
binding (NF-κB) signal pathway, resulting in the lowered production
of pro-inflammatory cytokines and the balancing of the immune homeostasis
with the prevention of macrophage infiltration in the liver. The regulation
of hepatic inflammation contributes to inhibiting inflammatory cytokines-induced
hepatocyte apoptosis, decreasing the serum alanine aminotransferase
(ALT) and aspartate aminotransferase (AST) contents and thus ameliorating
immune-mediated hepatic injury. Notably, there is no detectable toxicity
to the body. Our findings may open up novel avenues for AIH based
on curdlan and fullerene materials.