Lack of PPAR alpha exacerbates lipopolysaccharide-induced liver toxicity through STAT1 inflammatory signaling and increased oxidative/nitrosative stress

作者：Yoo Seong Ho; Park Ogyi; Henderson Lauren E; Abdelmegeed Mohamed A; Moon Kwan Hoon; Song Byoung Joon^*

来源：Toxicology Letters, 2011, 202(1): 23-29.

DOI：10.1016/j.toxlet.2011.01.013

• PPAR alpha
• Lipopolysaccharide
• Acute liver damage
• Cytokines
• STAT
• Oxidative/nitrosative stress

Peroxisome proliferator-activated receptor-alpha (PPAR alpha) has been implicated in a potent anti-inflammatory activity. However, no information is available on whether PPAR alpha can affect signal transducers and activator of transcription proteins (STATs) in acute liver damage. Thus, this study was aimed to investigate the in vivo role of PPAR alpha in elevating STATs as well as oxidative/nitrosative stress in a model of lipopolysaccharide (LPS)-induced acute hepatic inflammatory injury. Using age-matched Ppara-null and wild-type (WT) mice, we demonstrate that the deletion of PPAR alpha aggravates LPS-mediated liver injury through activating STAT1 and NF-KB-p65 accompanied by increased levels of pro-inflammatory cytokines. Furthermore, the activities of key anti-oxidant enzymes and mitochondrial complexes were significantly decreased while lipid peroxidation and protein nitration were elevated in LPS-exposed Ppara-null mice compared to WT. These results indicate that PPAR alpha is important in preventing LPS-induced acute liver damage by regulating STAT1 inflammatory signaling pathways and oxidative/nitrosative stress. Published by Elsevier Ireland Ltd.

• 出版日期2011-4-10