NADPH oxidase is not an essential mediator of oxidative stress or liver injury in murine MCD diet-induced steatohepatitis

dela Pena, Aileen;Leclercq, Isabelle;Williams, Jacqueline;Farrell, Geoffrey C.
(2007) Journal of Hepatology — Vol. 46, n° 2, p. 304-313 (2007)

Files

pdfdocument.pdf
  • Restricted Access
  • Adobe PDF
  • 2.51 MB
Request a copy

Details

Authors
  • dela Pena, Aileen
    Author
  • Leclercq, Isabelleorcid-logoUCLouvain
    Author
  • Williams, Jacqueline
    Author
  • Farrell, Geoffrey C.
    Author
Abstract
Background/Aims: Hepatic oxidative stress is a key feature of metabolic forms of steatohepatitis, but the sources of pro-oxidants are unclear. The NADPH oxidase complex is critical for ROS generation in inflammatory cells; loss of any one component (e.g., gp91(Phox)) renders NADPH oxidase inactive. We tested whether activated inflammatory cells contribute to oxidant stress in steatohepatitis. Methods: gp91(phox-/-) and wildtype (wt) mice were fed a methionine and choline-deficient (MCD) diet. Serum ALT, hepatic triglycerides, histopathology, lipid peroxidation, activation of NF-kappa B, expression of NF-kappa B-regulated genes and macrophage chemokines were measured. Results:After 10 days of MCD dietary feeding, gp91(phox-/-) and wt mice displayed equivalent hepatocellular injury. After 8 weeks, there were fewer activated macrophages in livers of gp91(phox-/-) mice than controls, despite similar mRNA levels for MCP and MIP chemokines, but fibrosis was similar. NF-kappa B activation and increased expression of ICAM-1, TNF-alpha and COX-2 mRNA were evident in both genotypes, but in gp91(phox-/-) mice, expression of these genes was confined to hepatocytes. Conclusions: A functional NADPH oxidase complex does not contribute importantly to oxidative stress in this model and therefore is not obligatory for induction or perpetuation of dietary steatohepatitis. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Affiliations

Citations

  • APA
  • Chicago
  • FWB

dela Pena, A., Leclercq, I., Williams, J., & Farrell, G. C. (2007). NADPH oxidase is not an essential mediator of oxidative stress or liver injury in murine MCD diet-induced steatohepatitis. Journal of Hepatology, 46(2), 304-313. https://doi.org/10.1016/j.jhep.2006.08.025 (Original work published 2007)