Abstract
Acetaminophen (APAP)-induced acute liver injury (ALI) is the principal cause of
acute liver failure (ALF) in some countries including the United States and with
few available treatments. Isorhamnetin is a bioflavonoid that is found in
medicinal plants like Hippophae rhamnoides L. and Ginkgo biloba L.
with promising potential to regulate inflammatory responses. In this study, we
evaluated the possible effect of isorhamnetin in prevention of APAP-induced ALI
and analyzed further the involvement of oxidative stress and
inflammation-associated factors. Male C57BL/6 mice were given
isorhamnetin (25 or 100 mg/kg b.w., p.o.) three times at
48, 24, and 1 h before APAP administration (300 mg/kg
b.w., i.p.). Functional indicators of liver injury were measured as well
as analysis of oxidative stress- and inflammation-associated indices and liver
histopathology was also conducted. Isorhamnetin at the higher dose of
100 mg/kg significantly lowered serum levels of ALT, ALP, and
AST in addition to reduction of ROS, TBARS, IL-6, TNFα, NF-kB, NLRP3,
caspase 1, and MPO and significantly prevented reduction of GSH, SOD activity,
sirtuin 1, and Nrf2. Additionally, isorhamnetin alleviated pathological changes
of the liver tissue and suitably reversed NF-kB and Nrf2 immunoreactivity. These
findings show protective effect of isorhamnetin against acetaminophen-induced
liver injury through reducing oxidative stress, inflammation, and pyroptosis
which is attributed to its regulation of NF-kB, Nrf2, NLRP3, and sirtuin 1.
Key words
Isorhamnetin - Acetaminophen - Acute liver injury - Hepatoprotective
