Intestinal injury in the rat model of 17α-ethynylestradiol-induced intrahepatic cholestasis.
OBJECTIVE
Although the intimate relationship between liver and gut has been previously reported under physiological and pathological conditions, intestinal involvement in the process of intrahepatic cholestasis of pregnancy remains unclear. The aim of this study was to investigate intestinal changes in 17α-ethynylestradiol (EE)-induced cholestatic rat model.


METHODS
Liver injury was assessed by HE stain and serum biochemical parameters were measured. Intestinal transit was determined using ink marks. Neuronal protein expressions in the intestine were analyzed by Western blot.


RESULTS
EE treatment induced liver damage, including severe bile duct hyperplasia, portal edema, portal infiltration, a loss of hepatic structure in periportal areas and increased serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and total bilirubin. Large areas of inflammatory cell infiltration and increased myeloperoxidase activity were observed in the intestine of EE-induced cholestatic rats. The EE-treated group showed increased intestinal transit and malondialdehyde levels, while the glutathione content and superoxide dismutase activity were notably decreased, together with decreased protein gene product 9.5 and neuronal nitric oxide synthase expression in the ileum and colon. Furthermore, choline acetyltransferase expression was significantly decreased in the ileum, whereas no change was observed in the colon of EE-treated rats.


CONCLUSIONS
EE-induced liver damage is associated with oxidative stress, inflammation and neural loss in the intestine, which may lead to altered intestinal motility.
Center for Translational Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Mu Jun
MJ
Chang
Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Yan Jiao
YJ
Xu
Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Wen Xi
WX
He
Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Cheng Liang
CL
Zhang
Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Xi Ping
XP
Li
Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Dong
D
Liu
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology* / Q000503:physiopathology; D002780:Cholestasis, Intrahepatic / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004997:Ethinyl Estradiol / Q000009:adverse effects / Q000494:pharmacology*; D005772:Gastrointestinal Transit / Q000187:drug effects; D007410:Intestinal Diseases / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D007422:Intestines / Q000187:drug effects / Q000294:innervation / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D008107:Liver Diseases / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009676:Noxae / Q000009:adverse effects / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats
D009676:Noxae; D004997:Ethinyl Estradiol
altered intestinal motility; enteric neural loss; intrahepatic cholestasis of pregnancy; oxidative stress