Hepatoprotective effect of SY-640, a novel acetamide derivative, on Propionibacterium acnes and lipopolysaccharide-induced liver injury in mice.
The hepatoprotective effect of SY-640 on Propionibacterium acnes and lipopolysaccharide-induced liver injury in mice and its protective mechanism were examined. Oral administration of SY-640, 150 mg/kg once daily for 7 days, significantly inhibited Propionibacterium acnes and lipopolysaccharide-induced liver injury, but a single administration was without effect. Liver-infiltrating cells (T-lymphocytes and macrophages) play an important role in Propionibacterium and lipopolysaccharide-induced liver injury and express a higher level of leukocyte function-associated antigen-1. SY-640 inhibited the number of liver-infiltrating cells and attenuated the increased expression of leukocyte function-associated antigen-1 on these cells. Tumor necrosis factor-alpha mediated Propionibacterium acnes and lipopolysaccharide-induced liver injury, and SY-640 inhibited the elevation of the serum tumor necrosis factor-alpha concentration after injection of lipopolysaccharide in Propionibacterium acnes-primed mice. The putative effects of SY-640 are inhibitory effects on infiltration into the liver and on activation of T-lymphocytes and macrophages after Propionibacterium acnes-priming, and attenuation of expression of cell adhesion molecules such as leukocyte function-associated antigen-1. The immunological effect of SY-640 is likely to be closely related to the inhibition of Propionibacterium and lipopolysaccharide-induced liver injury.
Tanaka
Y
Y
Department of Pharmacology, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Takahashi
A
A
Kobayashi
K
K
Arai
I
I
Higuchi
S
S
Otomo
S
S
Wei
H L
HL
Liu
G T
GT
D000081:Acetamides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism; D004396:Coloring Agents; D003470:Culture Media; D005434:Flow Cytometry; D007249:Inflammation / Q000188:drug therapy; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011425:Propionibacterium acnes / Q000187:drug effects*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000081:Acetamides; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D004396:Coloring Agents; D003470:Culture Media; D008070:Lipopolysaccharides; C097411:SY 640; D014409:Tumor Necrosis Factor-alpha