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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
environmental science
Depletion of Kupffer cells modulates ethanol-induced hepatocyte DNA synthesis in C57Bl/6 mice
Environmental Toxicology, Volume 29, No. 8, Year 2014
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Description
Kupffer cells (KCs) are important in hepatic homeostasis and responses to xenobiotics. KCs are activated on interaction with endotoxin, releasing cytokines, and reactive oxygen species normally associated with increased gene expression, cellular growth, or hepatic injury. Ethanol-induced endotoxemia is one means of KC activation. We propose that KC depletion attenuates the effect of EtOH-induced endotoxemia to impact the hepatic growth response. Hepatic DNA synthesis was examined in KC competent (KC+) or KC-depleted (KC-) C57BL/6 mice fed EtOH-containing diet in the presence or absence of polyphenol-60 antioxidant. KC depletion was assessed by F4/80 antigen, and DNA synthesis was assessed by 5-bromo-2'-deoxyuridine incorporation. Tumor necrosis factor alpha (TNF-α) messenger RNA released was quantified by RT-PCR/electrophoresis. ERK1/2 phosphorylation was evaluated by Western blotting, and Nrf2 and CYP2E1protein were also assayed. Apoptosis and hepatic injury were examined by the Tunnel assay and hepatic transaminases in serum, respectively. Hepatic transaminases in serum (AST and ALT) were within normal range. Over 90% of KC was depleted by clodronate treatment. KC depletion decreased TNF-α mRNA release, ERK1/2 phosphorylation, and hepatocyte DNA synthesis. KC depletion is associated with increased numbers of apoptotic cells bodies in KC- mice. Antioxidant treatment decreased DNA synthesis, Nrf2, and CYP2E1 protein expression in EtOH-consuming mice. Our data indicate that upon ethanol exposure, KC participates in hepatic DNA synthesis and growth responses. Collectively, these observations suggest that KC depletion attenuates the downstream effect of ethanol-induced endotoxemia by reduced cytokine and reactive oxygen species production with its concomitant effect on MAPK-signaling pathway on hepatocyte DNA synthesis. © 2012 Wiley Periodicals, Inc., a Wiley company.
Authors & Co-Authors
Owumi, Solomon Eduviere
Nigeria, Ibadan
University of Ibadan
United States, Palo Alto
Stanford University
Corthals, Stacy M.
United States, Indianapolis
Indiana University School of Medicine
Uwaifo, Anthony O.
Nigeria, Ibadan
University of Ibadan
Kamendulis, Lisa M.
United States, Indianapolis
Indiana University School of Medicine
Klaunig, James E.
United States, Indianapolis
Indiana University School of Medicine
Statistics
Citations: 11
Authors: 5
Affiliations: 3
Identifiers
Doi:
10.1002/tox.21814
ISSN:
15204081
e-ISSN:
15227278
Research Areas
Cancer
Genetics And Genomics
Violence And Injury