Hepatocytes regeneration

Finally/ there is evidence that Kupffer cells are a source of the anti-inflammatory cytokine interleukin-10 (IL-10) that may play an important protective role by minimizing formation of reactive nitrogen species when superoxide is released following MPT (24). Pro-inflammatory cytokines (e.g./ macrophage migration inhibitory factor) may exacerbate hepatocellular necrosiS/ whereas chemokines (e.g./ monocyte chemoattractant protein-1) appear to reduce the extent of hepatotoxicity and facilitate eventual hepatocyte regeneration in surviving patients (13). 

Lymphocytes in portal tracts and in the lobule Hepatocyte regeneration Cholestasis... 

Stem cell factor (SCF) and its receptor c-kit play an important role in hepatocyte regeneration and proliferation. APAP treatment results in increase SCF and the c-kit receptor expression in liver beginning at 6 h. Pathways activated by SCF include PI-3 kinase, Src family members, JAK/STAT, and Ras-Raf-MAPK cascade (Hu and Colletti 2008). SCF administration hours after APAP treatment resulted in increase hepatocyte proliferation and a reduction of APAP-induced liver injury. SCF treatment increased bcl-xl and bcl-2 expression in liver mitochondria,... 

Interleukin-6 (IL-6) has also been examined in acetaminophen toxicity. While it is known to be important in hepatocyte regeneration (discussed below), one study... 

Cressman DE, Greenbaum LE, DeAngelis RA, Ciliberto G, Furth EE, Poll V, Taub R (1996) Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice. Science 274 1379-1383... 

Janies LP, Lamps LW, McCullough S, Hinson JA (2003a) Interleukin 6 and hepatocyte regeneration in acetaminophen toxicity in the mouse. Biochem Biophys Res Commun 309 857-863 James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, Davem TJ, Lee WM (2009) Pharmacokinetics of acetaminophen-protein adducts in adults with acetaminophen ovtadose and acute liver failure. Drag Metab Dispos 37 1779-1784. Published online May 13, 2009 10.1124/dmd.l08.026195... 

From the experimental point of view it was shown that, in mice to which aqueous solutions of trecresan and mival (5 mg/L) were administered for 20 days, DNA and RNA content in live animals rose to 110.5 and 134.2 respectively against 98.6 in the test group. Use of trecresan in the partial hepatoectomy experiments in rats results in intensification of hepatocyte regeneration, a rise in macroergons and acceleration of individual phases of the mitotic cycle. These processes occur simultaneously with suppression of lipid peroxide oxidation in the hepatocytes and a decrease in oxygen transfer rate through mitochondrial membranes. Similar tests for the analysis of the... 

Oral exposure of rats to a single dose of 100 mg/kg carbon tetrachloride did not result in unscheduled DNA synthesis in hepatocytes isolated from the treated animals (Mirsalis and Butterworth 1980). The effect of other dose levels or repeated exposures was not investigated. In a similar experiment, Craddock and Henderson (1978) found that oral exposure of rats to carbon tetrachloride caused an increase in DNA synthesis associated with tissue regeneration, but no increase in unscheduled DNA synthesis. Furthermore, chromosome aberrations, micronuclei, or sister chromatid exchanges were not induced within 4-72 hours in hepatocytes take from rats treated with the relatively high dose of 1,600 mg/kg (Sawada et al. 1991). 

Lindroos PM, Zarnegar R, Michalopoulos GK. 1990. Hepatocyte growth factor (hepatopoietin A) rapidly increases in plasma before DMA synthesis and liver regeneration stimulated by partial hepatectomy and carbon tetrachloride administration. Hepatology 13 743-750. 

Thorgeirsson, S.S., Hepatic stem cells in liver regeneration. FASEB J. 10,1249,1996. Dunn, J., Tompkins, R., and Yarmush, M. Long term in vitro function of adult hepatocytes in a collagen sandwich configuration Biotechnol. Prog. 7.237,1991. Allen, J., Hassanien, T, and Bhatia, S. Advances in bioai tificial liver devices, Hepatology 34,447, 2001. 

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