title: Heme oxygenase/carbon monoxide pathway inhibition plays a role in ameliorating fibrosis following splenectomy.
abstract: Splenectomy is a recognized therapy for liver cirrhosis with splenomegaly, since it decreases free iron concentration that accompanies the destruction of red blood cells. Heme oxygenase (HO)-1 and its by-products, iron and carbon monoxide (CO), play crucial roles in hepatic fibrosis. The aim of the present study was to determine whether splenectomy in cirrhotic rats induced by bile duct ligation (BDL), through the HO/CO pathway, could slow down the development of liver fibrosis. Male Sprague-Dawley rats were divided randomly into the sham, BDL, splenectomy, Fe, zinc protoporphyrin (Znpp) and cobalt protoporphyrin (Copp) treatment groups, for inhibiting and inducing HO-1 expression. The level of HO-1 was detected by western blot analysis and reverse transcription-polymerase chain reaction. Serum carboxyhemoglobin (COHb), iron and portal vein pressure (PVP) were also quantified. Liver iron was measured by atomic absorption spectrometry with acetylene-air flame atomization. HO-1 and α-smooth muscle actin (α-SMA) were localized by immunohistochemistry. Liver and spleen iron were visualized by Perls' Prussian blue staining. Hepatic fibrosis was assessed using hematoxylin and eosin (H&E) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum transforming growth factor-β1 (TGF-β1). The results showed that liver, spleen and serum levels of HO-1, COHb and iron were greatly enhanced in the BDL group compared with the sham group; they were reduced following splenectomy and Znpp treatment, but were elevated in the Copp and Fe groups. Hydroxyproline, TGF-β1, α-SMA, PVP and malonaldehyde levels were lower in the splenectomy and Znpp groups compared to BDL, while higher levels were observed in the Copp and Fe-treated groups. Our study shows that splenectomy reduces iron and CO levels in part by reducing HO-1 expression, and it decreases portal pressure and slightly decreases hepatic fibroproliferation.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Qiu-Ming
authors.initials: QM
authors.lastname: Wang
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Duan
authors.forename: Jian-Ling
authors.initials: JL
authors.lastname: Du
authors.forename: Shi-Bin
authors.initials: SB
authors.lastname: Guo
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Sun
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000473:pathology / Q000503:physiopathology; D001835:Body Weight; D002248:Carbon Monoxide / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D008026:Ligation; D008099:Liver / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009929:Organ Size; D018384:Oxidative Stress; D017082:Portal Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013154:Spleen / Q000473:pathology / Q000601:surgery; D013156:Splenectomy / Q000009:adverse effects*
chemical_list: D002248:Carbon Monoxide; D007501:Iron; D051547:Heme Oxygenase-1