Dai-kenchu-to attenuates rat sinusoidal obstruction syndrome by inhibiting the accumulation of neutrophils in the liver.
OBJECTIVE
Sinusoidal obstruction syndrome (SOS) is drug-induced liver injury that occurs in patients who receive hematopoietic cell transplantation and oxaliplatin-contained chemotherapy. The aim of study was to investigate the pharmacological treatment of SOS using a traditional Japanese medicine, Dai-kenchu-to (DKT).


METHODS
Male Sprague-Dawley rats were treated with monocrotaline (MCT) to induce SOS. The rats were divided into three groups: control, MCT and MCT+DKT groups. In the MCT+DKT group, DKT was gavaged at 12 h after MCT treatment and given every 12 h until the end of the protocol. The rats of MCT group were treated with water instead of DKT. At 48 h after MCT treatment, blood and liver samples were collected.


RESULTS
In the MCT+DKT group, the macroscopic and histological findings revealed liver congestion, sinusoidal alteration and the destruction of sinusoidal lining, which were comparable with those of the MCT group. However, the area of hepatic necrosis and serum AST levels significantly decreased in the MCT+DKT group compared with those of the MCT group. Treatment with DKT resulted in the reduction of neutrophil accumulation, myeloperoxidase activity and the expression of cytokine-induced neutrophil chemoattractant (CINC) and intracellular adhesion molecule-1 (ICAM-1) mRNA in the liver compared with those of the MCT group. Treatment with processed ginger, one of the ingredients in DKT, resulted in similar effects to those shown by DKT.


CONCLUSIONS
Dai-kenchu-to attenuates MCT-induced liver injury by preventing neutrophil-induced liver injury through blockage of upregulation of CINC and ICAM-1 mRNA level.
Narita
Masato
M
Department of Surgery, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
Hatano
Etsuro
E
Tamaki
Nobuyuki
N
Yamanaka
Kenya
K
Yanagida
Atsuko
A
Nagata
Hiromitsu
H
Asechi
Hiroyuki
H
Takada
Yasutsugu
Y
Ikai
Iwao
I
Uemoto
Shinji
S
D000818:Animals; D054360:Chemokine CXCL1 / Q000378:metabolism; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D016686:Monocrotaline; D009504:Neutrophils / Q000187:drug effects; D005894:Panax; D009195:Peroxidase / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D015854:Up-Regulation; D032106:Zanthoxylum; D030521:Zingiberaceae
D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D010936:Plant Extracts; D012333:RNA, Messenger; C121414:dai-kenchu-to; D018799:Intercellular Adhesion Molecule-1; D016686:Monocrotaline; D009195:Peroxidase