Can a flavonoid rescue acetaminophen livers via GPX4?
In C57BL/6 mice, Thonningianin A (20–40 mg/kg) before APAP 300 mg/kg cut ALT/AST and ER-stress markers, but AAV8 liver GPX4 knockdown (53.6% protein loss) abolished protection.
Source
Thonningianin A ameliorates acetaminophen-induced liver injury by activating GPX4 and modulating endoplasmic reticulum stress
Study at a glance
- Design
- Animal / in-vitro — C57BL/6 mice, oral Thonningianin A 20/40 mg/kg then APAP 300 mg/kg; AAV8 hepatocyte GPX4 shRNA knockdown
- N
- N=8 · Biochemistry figures report mean ± SD, n = 5–8 mice per group
- Population
- 8-week C57BL/6 mice with or without liver-targeted AAV8-GPX4 shRNA, plus APAP hepatotoxicity
- Outcome
- Plasma ALT/AST, hepatic cytokines/oxidative-stress markers, apoptosis and ER-stress proteins, dependence on GPX4
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Inspect source passages
Can a flavonoid rescue acetaminophen livers via GPX4?
These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.
TA was given at 20 and 40 mg/kg before APAP in C57BL/6 mice.
administering TA at doses of 20 mg/kg and 40 mg/kg to C57BL/6 mice prior to inducing hepatotoxicity with APAP
APAP challenge was 300 mg/kg i.p.
they were intraperitoneally injected with 300 mg/kg of APAP
What they did
Pretreated mice with oral TA 20 or 40 mg/kg, then i.p. APAP 300 mg/kg; measured ALT/AST, cytokines, apoptosis/ER-stress proteins, and repeated the APAP+TA experiment after hepatocyte GPX4 shRNA (AAV8).
What they found
TA lowered ALT/AST, IL-1β/IL-6/TNF-α/MCP-1, raised BCL-2, and cut CHOP/BAX, GRP78, p-PERK, and ATF4. GPX4 knockdown (53.6% protein drop) raised ALT/AST again despite TA.
The limits
What it doesn't show
Mouse APAP overdose is not a registered human trial of TA; n=5–8/group cannot define a clinical dose, and GPX4 knockdown does not prove TA binds GPX4 directly.
Key terms
- Thonningianin A
- Flavonoid from Penthorum chinense tested against APAP hepatotoxicity.
- APAP
- Acetaminophen; 300 mg/kg i.p. induced acute liver injury here.
- GPX4
- Glutathione peroxidase 4; lipid-peroxide reducing enzyme required for TA’s protection.
- ER stress
- Unfolded-protein response; TA lowered GRP78, p-PERK, and ATF4.
- ALT/AST
- Plasma transaminases used as liver-injury readouts.
- AAV8 shRNA
- Liver-tropic viral knockdown of hepatocyte GPX4.
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Quiz yourself
TA was tested mainly in:
Common questions
What TA doses were used?
20 and 40 mg/kg orally, 2 h before APAP.
What APAP dose induced injury?
300 mg/kg intraperitoneally.
Did GPX4 knockdown matter?
Yes—it abolished TA’s hepatoprotection.
How large was GPX4 protein loss?
53.6% by Western blot.
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