PMID- 31902937
OWN - NLM
STAT- MEDLINE
DCOM- 20201109
LR  - 20201109
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 43
IP  - 1
DP  - 2020
TI  - Repeated Administration of Kupffer Cells-Targeting Nanoantioxidant Ameliorates 
      Liver Fibrosis in an Experimental Mouse Model.
PG  - 93-101
LID - 10.1248/bpb.b19-00599 [doi]
AB  - Kupffer cells are a major producer of reactive oxygen species and have been 
      implicated in the development of liver fibrosis during chronic hepatitis in 
      non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH). We 
      recently reported on the development of a polythiolated and mannosylated human 
      serum albumin (SH-Man-HSA) that functions as a Kupffer cell-targeting 
      nanoantioxidant. In this material, the albumin is mannosylated, which permits it 
      to be taken up by mannose receptor C type 1 expressed on Kupffer cells, and is 
      also polythiolated to have antioxidant activity. To clarify the anti-fibrotic 
      property of this nanoantioxidant, we repeatedly administered SH-Man-HSA to a 
      liver fibrosis mouse model that was induced by the repeated treatment of the 
      concanavalin-A, which mimics the liver fibrosis observed in NASH and ASH. 
      SH-Man-HSA dramatically improved the survival rate and suppressed liver fibrosis 
      in the experimental model. In addition, SH-Man-HSA suppressed hepatic oxidative 
      stress levels, thereby decreasing the numbers of apoptotic cells. In contrast, 
      N-acetylcysteine, which contains the same thiol content as the SH-Man-HSA, failed 
      to show a substantial therapeutic effect in these mice. The expression levels of 
      inflammatory genes including epidermal growth factor module-containing mucin-like 
      receptor (Emr-1/F4/80), Toll-like receptor-4 (TLR-4), high mobility group box-1 
      (HMGB-1), CC chemokine ligand-5 (CCL-5), tumor necrosis factor-alpha (TNF-alpha), CCL-2, 
      interleukin-6 (IL-6), and IL-1beta, as well as fibrotic (alpha-smooth muscle actin 
      (alpha-SMA), transforming growth factor-beta (TGF-beta), and Snail) and extracellular 
      matrix genes (collagen, type Ialpha2 (Col1alpha2), matrix metalloproteinase-9 (MMP-9), 
      and tissue inhibitor of metalloproteinase 1 (TIMP-1)), showed some decreasing 
      trends by the SH-Man-HSA administration. These findings suggest that the repeated 
      administration of the Kupffer cell-targeting nanoantioxidant, SH-Man-HSA, 
      ameliorates liver fibrosis in mice by suppressing the level of oxidative stress 
      and a portion of the inflammation, and has a potential therapeutic effect against 
      NASH and ASH.
FAU - Maeda, Hitoshi
AU  - Maeda H
AD  - Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, 
      Kumamoto University.
FAU - Minayoshi, Yuki
AU  - Minayoshi Y
AD  - Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, 
      Kumamoto University.
FAU - Ichimizu, Shota
AU  - Ichimizu S
AD  - Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, 
      Kumamoto University.
FAU - Mizuta, Yuki
AU  - Mizuta Y
AD  - Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, 
      Kumamoto University.
FAU - Nagasaki, Taisei
AU  - Nagasaki T
AD  - Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, 
      Kumamoto University.
FAU - Matsusaka, Kotaro
AU  - Matsusaka K
AD  - Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, 
      Kumamoto University.
FAU - Oshiro, Shun
AU  - Oshiro S
AD  - Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, 
      Kumamoto University.
FAU - Oniki, Kentaro
AU  - Oniki K
AD  - Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical 
      Sciences, Kumamoto University.
FAU - Saruwatari, Junji
AU  - Saruwatari J
AD  - Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical 
      Sciences, Kumamoto University.
FAU - Ishima, Yu
AU  - Ishima Y
AD  - Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical 
      Sciences, Tokushima University.
FAU - Watanabe, Hiroshi
AU  - Watanabe H
AD  - Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, 
      Kumamoto University.
FAU - Otagiri, Masaki
AU  - Otagiri M
AD  - Faculty of Pharmaceutical Sciences and DDS Research Institute, Sojo University.
FAU - Maruyama, Toru
AU  - Maruyama T
AD  - Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, 
      Kumamoto University.
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Albumins)
RN  - 0 (Antioxidants)
RN  - 0 (Glycoproteins)
RN  - 0 (SH-Man-HSA protein)
RN  - 11028-71-0 (Concanavalin A)
SB  - IM
MH  - Albumins/*therapeutic use
MH  - Animals
MH  - Antioxidants/*therapeutic use
MH  - Concanavalin A
MH  - Disease Models, Animal
MH  - Fatty Liver, Alcoholic/*drug therapy/genetics
MH  - Female
MH  - Gene Expression/drug effects
MH  - Glycoproteins/*therapeutic use
MH  - Kupffer Cells/drug effects/metabolism
MH  - Liver Cirrhosis/chemically induced/*drug therapy/genetics
MH  - Mice, Inbred BALB C
MH  - Non-alcoholic Fatty Liver Disease/*drug therapy/genetics
MH  - Oxidative Stress/drug effects
OTO - NOTNLM
OT  - antioxidant
OT  - chronic hepatitis
OT  - liver fibrosis
OT  - reactive oxygen species
EDAT- 2020/01/07 06:00
MHDA- 2020/11/11 06:00
CRDT- 2020/01/07 06:00
PHST- 2020/01/07 06:00 [entrez]
PHST- 2020/01/07 06:00 [pubmed]
PHST- 2020/11/11 06:00 [medline]
AID - 10.1248/bpb.b19-00599 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2020;43(1):93-101. doi: 10.1248/bpb.b19-00599.