Reliable experimental model of hepatic veno-occlusive disease caused by monocrotaline.
BACKGROUND
Hepatic veno-occlusive disease (HVOD) is a severe complication of chemotherapy before hematopoietic stem cell transplantation and dietary ingestion of pyrrolizidine alkaloids. Many experimental models were established to study its mechanisms or therapy, but few are ideal. This work aimed at evaluating a rat model of HVOD induced by monocrotaline to help advance research into this disease.


METHODS
Thirty-two male rats were randomly classified into 5 groups, and PBS or monocrotaline was administered (100 mg/kg or 160 mg/kg). They were sacrificed on day 7 (groups A, B and D) or day 10 (groups C and E). Blood samples were collected to determine liver enzyme concentrations. The weight of the liver and body and the amount of ascites were measured. Histopathological changes of liver tissue on light microscopy were assessed by a modified Deleve scoring system. The positivity of proliferating cell nuclear antigen (PCNA) was estimated.


RESULTS
The rats that were treated with 160 mg/kg monocrotaline presented with severe clinical symptoms (including two deaths) and the histopathological picture of HVOD. On the other hand, the rats that were fed with 100 mg/kg monocrotaline had milder and reversible manifestations. Comparison of the rats sacrificed on day 10 with those sacrificed on day 7 showed that the positivity of PCNA increased, especially that of hepatocytes.


CONCLUSIONS
Monocrotaline induces acute, dose-dependent HVOD in rats. The model is potentially reversible with a low dose, but reliable and irreversible with a higher dose. The modified scoring system seems to be more accurate than the traditional one in reflecting the histopathology of HVOD. The enhancement of PCNA positivity may be associated with hepatic tissue undergoing recovery.
Chen
Miao-Yan
MY
Department of Gastroenterology and Hepatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
Cai
Jian-Ting
JT
Du
Qin
Q
Wang
Liang-Jing
LJ
Chen
Jia-Min
JM
Shao
Li-Ming
LM
D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008115:Liver Regeneration; D008297:Male; D016686:Monocrotaline; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013997:Time Factors
D018809:Proliferating Cell Nuclear Antigen; D016686:Monocrotaline