Curdlan-Decorated Fullerenes Mitigate Immune-Mediated Hepatic Injury for Autoimmune Hepatitis Therapeutics via Reducing Macrophage Infiltration.
Chenglong FeiLei LiuHedong QiYuyang PengJingfen HanChun-Ru WangXue LiPublished in: ACS applied materials & interfaces (2024)
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.
Keyphrases
- oxidative stress
- nuclear factor
- diabetic rats
- drug induced
- adipose tissue
- toll like receptor
- signaling pathway
- mouse model
- liver injury
- ischemia reperfusion injury
- reactive oxygen species
- dna damage
- high glucose
- induced apoptosis
- healthcare
- multiple sclerosis
- palliative care
- reduced graphene oxide
- gene expression
- quantum dots
- type diabetes
- anti inflammatory
- high dose
- transcription factor
- early onset
- gold nanoparticles
- quality improvement
- inflammatory response
- glycemic control
- binding protein
- body mass index
- heat stress
- genome wide identification
- visible light