Protective effect and mechanism of stronger neo-minophagen C against fulminant hepatic failure.
OBJECTIVE
To investigate the protective effect of stronger neo-minophafen C (SNMC) on fulminant hepatic failure (FHF) and its underlying mechanism.


METHODS
A mouse model of FHF was established by intraperitoneal injection of galactosamine (D-Gal N) and lipopolysaccharide (LPS). The survival rate, liver function, inflammatory factor and liver pathological change were obtained with and without SNMC treatment. Hepatocyte survival was estimated by observing the stained mitochondria structure with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method and antibodies against cytochrome C (Cyt-C) and caspase-3.


RESULTS
The levels of plasma tumor necrosis factor alpha (TNF-alpha), nitric oxide (NO), ET-1, interleukin-6 (IL-6), and the degree of hepatic tissue injury were decreased in the SNMC-treated groups compared with those in the model group (P < 0.01). However, there were no differences after different dosages administered at different time points. There was a significant difference in survival rates between the SNMC-treated groups and the model group (P < 0.01). The apoptosis index was 32.3% at 6 h after a low dose of SNMC, which was considerably decreased from 32.3% +/- 4.7% vs 5% +/- 2.83% (P < 0.05) to 5% on d 7. The expression of Cyt-C and caspase-3 decreased with the prolongation of therapeutic time. Typical hepatocyte apoptosis was obviously ameliorated under electron microscope with the prolongation of therapeutic time.


CONCLUSIONS
SNMC can effectively protect liver against FHF induced by LPS/D-Gal N. SNMC can prevent hepatocyte apoptosis by inhibiting inflammatory reaction and stabilizing mitochondria membrane to suppress the release of Cyt-C and sequent activation of caspase-3.
Yang
Bao-Shan
BS
Department of Infectious Diseases, the First Clinical Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China.
Ma
Ying-Ji
YJ
Wang
Yan
Y
Chen
Li-Yan
LY
Bi
Man-Ru
MR
Yan
Bing-Zhu
BZ
Bai
Lu
L
Zhou
Hui
H
Wang
Fu-Xiang
FX
D000410:Alanine Transaminase / Q000378:metabolism; D000418:Albumins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001663:Bilirubin / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D003545:Cysteine / Q000494:pharmacology / Q000627:therapeutic use*; D045304:Cytochromes c / Q000378:metabolism; D004338:Drug Combinations; D019332:Endothelin-1 / Q000378:metabolism; D005260:Female; D005998:Glycine / Q000494:pharmacology / Q000627:therapeutic use*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000648:ultrastructure; D017114:Liver Failure, Acute / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008854:Microscopy, Electron; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000418:Albumins; D004338:Drug Combinations; D019332:Endothelin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C083319:stronger neominophagen C; D045304:Cytochromes c; D000410:Alanine Transaminase; D053148:Caspase 3; D003545:Cysteine; D006034:Glycyrrhetinic Acid; D001663:Bilirubin; D005998:Glycine