Laennec protects murine from concanavalin A-induced liver injury through inhibition of inflammatory reactions and hepatocyte apoptosis.
The effect of Laennec, a hydrolyte of human placenta, on immune-mediated liver injury was investigated in vivo and in vitro in murine. Vena caudalis administration of concanavalin A (Con A) was employed to establish an in vivo liver-injury model, and in vitro hepatotoxicity was induced by 8 h interaction between Con A pre-treated hepatocytes and Con A-stimulated autologous splenic lymphocytes. Laennec was used for pre-treatment in the two models. Laennec decreased biochemical marker activity (alanine aminotransferase, ALT; lactate dehydrogenase, LDH) in serum and recovered the activity of superoxide dismutase (SOD) and myeloperoxidase (MPO), as well as the content of malondialdehyde (MDA) and nitric oxide (NO) in liver tissue. We also found that the DNA ladder induced by Con A in vivo was attenuated by Laennec. Furthermore, the leakage of aspartate aminotransferase (AST) and LDH in the supernatant of the co-culture system was decreased by addition of Laennec. Potential protective mechanisms were elucidated by DNA fragmentation assay and intercellular adhesion molecule-1 (ICAM-1) induction/inhibition experiments. Results showed that ICAM-1, which is related to the interaction between hepatocytes and lymphocytes, was inhibited by Laennec. These findings indicated that Laennec has potent activity against immune-mediated liver injury.
Wu
Jingjing
J
Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, PR China.
Yang
Tao
T
Wang
Changyuan
C
Liu
Qi
Q
Yao
Jihong
J
Sun
Huijun
H
Kaku
Tai-Ichi
T
Liu
Ke-Xin
KX
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D003208:Concanavalin A; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004247:DNA / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010920:Placenta / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014020:Tissue Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D015415:Biomarkers; D014020:Tissue Extracts; D003208:Concanavalin A; D018799:Intercellular Adhesion Molecule-1; D004247:DNA