NADPH oxidase is not an essential mediator of oxidative stress or liver injury in murine MCD diet-induced steatohepatitis.
Date
2007
Authors
dela Pena, Aileen
Leclercq, Isabelle A
Williams, Jacqueline
Farrell, Geoffrey
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Elsevier
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., gp91phox) renders NADPH oxidase inactive. We tested whether activated inflammatory cells contribute to oxidant stress in steatohepatitis. Methods: gp91phox-/- and wildtype (wt) mice were fed a methionine and choline-deficient (MCD) diet. Serum ALT, hepatic triglycerides, histopathology, lipid peroxidation, activation of NF-κB, expression of NF-κB-regulated genes and macrophage chemokines were measured. Results: After 10 days of MCD dietary feeding, gp91phox-/- and wt mice displayed equivalent hepatocellular injury. After 8 weeks, there were fewer activated macrophages in livers of gp91phox-/- mice than controls, despite similar mRNA levels for MCP and MIP chemokines, but fibrosis was similar. NF-κB activation and increased expression of ICAM-1, TNF-α and COX-2 mRNA were evident in both genotypes, but in gp91phox-/- 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.
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Keywords: alanine aminotransferase; chemokine; choline; cyclooxygenase 2; glycoprotein gp 91; immunoglobulin enhancer binding protein; intercellular adhesion molecule 1; messenger RNA; methionine; reduced nicotinamide adenine dinucleotide phosphate oxidase; triacyl gp91 phox; Inflammation; MCD diet; NF-?B; Non-parenchymal cells; Oxidant stress
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Journal of Hepatology
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Journal article
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2037-12-31
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