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The pro‐fibrotic effects of pregnancy in a carbon‐tetrachloride‐induced liver injury in mouse model
Author(s) -
Amer Johnny,
Grifat Rami,
Doron Sarit,
AbuTair Lina,
Mruwat Rufayda,
ElKhatib Areej,
Safadi Rifaat
Publication year - 2014
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12371
Subject(s) - sirius red , hepatic stellate cell , liver injury , carbon tetrachloride , fibrosis , medicine , trichrome stain , pregnancy , kupffer cell , pathology , endocrinology , andrology , immunology , chemistry , biology , immunohistochemistry , organic chemistry , genetics
Background & Aims Immune cells interact with hepatic‐stellate‐cells ( HSC s) in the development of liver fibrosis. Little is known about the influence of pregnancy on the development and progression of hepatic‐fibrosis. In this study, we explored the influence of pregnancy on progression of hepatic fibrosis. Methods Female mice (C57Blc) were induced by 4 injections of peritoneal carbon‐tetrachloride ( CC l4) within 10 days, starting at day 10 of documented pregnancy. At end of experiment, serum samples were obtained for ALT and estradiol determination. Harvested livers were histological evaluated for liver injury and for protein α SMA expressions. Isolated intra‐hepatic lymphocytes were assessed by flow cytometry. Isolated lymphocytes and serum samples were in‐ vitro co‐cultured for 48 h with primary isolated naïve HSC s. Washed cells were analyzed for adherence (anti‐α SMA +/anti‐ CD 45 + ) and proliferations ( CSFE ). Results CCl4‐model for liver injury was well tolerated when induced in pregnancy similar to non‐pregnant state. Hepatic‐fibrosis (Masson Trichrome Stain, Sirius red stain and αSMA expressions) and necro‐inflammation (H&E stain and serum ALT levels) significantly increased in pregnancy. Increased liver injury was accompanied with pro‐fibrotic lymphocyte profile; CD8 subsets increased and NK cells decreased. HSCs activation significantly increased when in‐vitro cultured with lymphocytes from pregnant as compared to non‐pregnant fibrotic ones. Pro‐fibrotic profile was also explained by decreased NK activity (CD107a marker) and of their phagocytosis. Serum estradiol levels although elevated in fibrosis conditions of pregnancy was not associated with the pHSC s activations. Conclusion Liver fibrosis in our murine model was severe in pregnant model; via pro‐fibrotic lymphocyte and serum alterations.