Apolipoprotein A5 alleviates LPS/D-GalN-induced fulminant liver failure in mice by inhibiting TLR4-mediated NF-kappaB pathway.
MouseEndotoxin/LPSBalb/cMalen = n=3 per group for mechanistic and dose-response groups; sur…Tail vein injection5, 10 or 20 micrograms of pEGF-N1-ApoA5 plasmid per mouseThree days before LPS and D-galactosamine administration
Model: Fulminant liver failure induced by simultaneous intraperitoneal injection of lipopolysaccharide (20 micrograms/kg, rising to 30 and 40 micrograms/kg in dose-response work) and D-galactosamine (900 mg/kg)
ApoA5 overexpression lowered serum alanine aminotransferase and TNF-alpha, reduced hepatic necrosis and inflammatory infiltration, and suppressed TLR4, MyD88 and NF-kappaB p65. Twelve-hour survival was 70% with plasmid versus 40% with empty vector and 30% with saline, with a dose-dependent benefit…
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