FR167653 attenuates murine immunological liver injury.
OBJECTIVE
To study the effect of FR167653 on immunological liver injury (ILI) in mice.


METHODS
ILI was established by tail vein injection of 2.5 mg Bacillus Calmette-Guerin (BCG), and 10 d later with 10 mg lipopolysaccharide (LPS) in 0.2 mL saline (BCG plus LPS). Alanine aminotransferase (ALT), aspartate aminotransferase (AST) in sera and malondialdehyde (MDA), glutathione peroxidase (GSHpx) contents in liver homogenates were assayed by spectrophotometry. The levels of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) levels in sera were determined using ELISA. Interleukin-1 (IL-1) produced by peritoneal macrophages was determined by the method of (3)H-infiltrated cell proliferation. The nuclear factor-kappa B (NF-kappaB) p65 in liver tissue was analyzed with reverse transcription polymerase chain reaction (RT-PCR). Liver samples collected were stained with hematoxylin and eosin.


RESULTS
FR167653 (50, 100, 150 mg/kg) could significantly decrease the serum transaminase (ALT, AST) activity and MDA content in liver homogenate, and improve reduced GSHpx level of liver homogenate. Liver histopathological examination showed FR167653 (100, 150 mg/kg) significantly reduced inflammatory cells infiltration and liver cells necrosis. FR167653 (50, 100, 150 mg/kg) significantly lowered TNF-alpha and NO levels in serum, and IL-1 produced by peritoneal macrophages. Moreover, expression of NF-kappaB mRNA in liver tissue of ILI induced by BCG plus LPS was significantly reduced by FR167653.


CONCLUSIONS
All results showed that FR167653 had significant inhibitory action on ILI in mice.
Yao
Hong-Wei
HW
Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, School of Medicine, Zhejiang University, Hangzhou 310031, Zhejiang Province, China. yhgwei@hotmail.com
Li
Jun
J
Chen
Ji-Qiang
JQ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008107:Liver Diseases / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D009163:Mycobacterium bovis / Q000276:immunology*; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; C104334:FR 167653; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D011720:Pyrazoles; D011725:Pyridines