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Fang B, Luo S, Song Y, Li N, Li H, Zhao RC: Intermittent dosing of G-CSF to ameliorate carbon tetrachloride-induced liver fibrosis in mice. Toxicology. 2010 Mar 30;270(1):43-8. Epub 2009 Dec 11. On the basis of the recent report that granulocyte colony-stimulating factor (G-CSF) administration after rats' partial orthotopic liver transplantation greatly improved survival rate and liver regeneration of partial graft, we here evaluated the effect of intermittent administration of G-CSF on fibrosis formation induced by carbon tetrachloride (CCl (4)). Bone marrow chimeric female C57BL/6 mice were treated with G-CSF at days 1, 7, 14, 21, and 28 after CCl (4) challenge. At day 35 after CCl (4) administration, we found that G-CSF treatment significantly reduced CCl (4)-induced liver damage and collagen deposition. In addition, levels of hepatic hydroxyproline and serum fibrosis markers in mice receiving G-CSF administration after CCl (4) challenge were significantly lower compared to those of control mice. Histological examination suggested that hepatic damage recovery was much better in these G-CSF-treated mice. Immunofluorescence and fluorescence in situ hybridization (FISH) analysis revealed that donor cells engrafted into host liver, had epithelium-like morphology and expressed albumin, although at low frequency. These results suggest that intermittent G-CSF treatment might initiate endogenous hepatic tissue regeneration in response to CCl (4) injury and ameliorate its fibrogenic effects. |
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