The roles of Kupffer cells in the development and regression of liver fibrosis / 药学学报

Hepatic fibrosis results from iterative hepatic injury with sustained inflammation, formation of scar tissue, loss of tissue architecture and organ failure. There is no doubt, from both human and animal studies, that too much or too protracted inflammation in the liver leads to excess scarring. During liver injury, Kupffer cells can quickly flood the hepatic milieu with soluble mediators, including oxidants, cytokines, and proteinases, which can affect stellate cell proliferation, migration, and differentiation. On the other hand, the contribution of Kupffer cells to regression of hepatic fibrosis has been demonstrated. These findings underscore the potential importance of hepatic macrophages in regulating both stellate cell biology and extracellular material degradation during regression of hepatic fibrosis. Therefore, biological characterization of Kupffer cells, their interactions with stellate cells in the cytokine environment are essential to understand the mechanisms underlying the progressive development of excessive scarring in the liver as well as the ability of the liver for tissue repair and recovery.

Fast evaluation of oxidative DNA damage by liquid chromatography-electrospray tandem mass spectrometry coupled with precision-cut rat liver slices / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To establish a fast and sensitive method for the detection of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in precision-cut rat liver slices by HPLC-MS/MS and to investigate isoniazid (INH) -induced oxidative DNA damage.</p><p><b>METHODS</b>Precision-cut liver slices (300 microm) were prepared from male rats, and incubated with INH (0.018 mol/L) for 2 h after 1 h preincubation. DNA in the slices was extracted and digested into free nucleosides at 37 degrees C. The samples were injected into HPLC-MS/MS after the proteins were removed. The level of oxidative DNA damage was estimated using the ratio of 8-OHdG to deoxyguanosine (dG).</p><p><b>RESULTS</b>The limit of detection of 8-OHdG was 1 ng/mL (S/N=3) and the intra-assay relative standard variation was 3.38% when one transition 284.3/168.4 was used as a quantifier and another two transitions 284.3/140.2, 306.1/190.2 as qualifiers. 8-OHdG and dG were well separated, as indicated by elution at 10.02 and 7.37 min, respectively. INH significantly increased the ratio of 8-OHdG to dG in rat liver slices (P<0.05).</p><p><b>CONCLUSION</b>8-OHdG in precision-cut liver slices could be sensitively determined by HPLC-MS/MS. HPLC-MS/MS coupled with precision-cut tissue slices is a fast and reliable analytical technique to evaluate oxidative DNA damage of target tissues caused by procarcinogens and cytotoxins.</p>