Concept · medicine
Ferroptosis
5 studies
Ferroptosis is iron-dependent regulated cell death driven by phospholipid peroxidation—distinct from apoptosis—often tracked through ACSL4-enriched oxidizable membranes and GPX4-dependent peroxide detoxification.
Students meet ferroptosis in both organ-injury and cancer contexts. Critical-care models ask whether restraining ferroptosis protects tissue; oncology asks whether triggering it kills resistant cells. Those are opposite therapeutic directions on the same pathway.
Studies
5
Findings
5
5 supporting · 0 challenging · 6 qualifying citations
Open tensions
3
Currently
What we know
- Dexmedetomidine can protect mouse kidneys after I/R in an ACSL4/ferroptosis-linked framing.
- Sepsis ALI literature treats ferroptosis as one interconnected injury program among others.
- Triggering tumor ferroptosis can help checkpoint therapy in cold tumors (preclinical).
- Blocking IRE1/JNK can attenuate ferroptosis-linked renal I/R injury in mice/cells.
- Valproic acid can restrain cisplatin-induced tubular ferroptosis in mice, unlike cisplatin’s tumor-ferroptosis story.
Largest unresolved question
A mouse renal I/R pharmacologic result and a sepsis ALI pathway review do not establish how much ferroptosis dominates human critical illness versus apoptosis/pyroptosis.
Common misconceptions
Ferroptosis is just another name for apoptosis.
It is iron-dependent lipid-peroxidation death with distinct regulators (e.g., ACSL4/GPX4).
Any drug that mentions ferroptosis is proven in patients.
Many claims remain preclinical; human contribution vs other death modes is still debated.
Ferroptosis drugs always protect tissue.
Oncology strategies may deliberately induce ferroptosis; organ-injury models often try to block it.
Claim ledger
What the evidence shows
Drawn from 5 studies in this library. Mix labels say which citation roles are present; they are not a strength score. Supports means evidence for a finding; Challenges means evidence against a stated position; Qualifies marks scope.
Dexmedetomidine can protect mouse kidneys after I/R in an ACSL4/ferroptosis-linked framing.
In a renal ischemia/reperfusion mouse model, dexmedetomidine improved Scr/BUN and was tested as acting by inhibiting ACSL4-linked ferroptosis and inflammation via α2-AR signaling.
- Which cell-death programs drive septic acute lung injury?— pathway review across autophagy/ferroptosis/pyroptosis — not the same Dex I/R experiment
Study Role Design N Population Outcome Does ICU sedative Dex blunt kidney ferroptosis after I/R? Supports Animal / in-vitroMouse bilateral renal I/R (45 min/48 h) plus HEK293T OGD/R with Dex and ACSL4/α2-AR manipulations Multiple animal/cell assay groups; no single primary clinical N C57BL/6 mice and HEK293T cells under renal I/R or OGD/R stress Ferroptosis, inflammation, and ACSL4 signaling after Dex via α2-AR Which cell-death programs drive septic acute lung injury? Qualifiespathway review across autophagy/ferroptosis/pyroptosis — not the same Dex I/R experiment OtherNarrative mechanistic review of autophagy, ferroptosis, and pyroptosis literature in LPS/CLP sepsis-induced ALI (not a new primary experiment) No primary analytic N; synthesizes published LPS/CLP and related studies Published preclinical (and cited clinical framework) literature on sepsis-induced ALI/ARDS Mapped death-pathway mechanisms and candidate pharmacologic targets for septic lung injury Sepsis ALI literature treats ferroptosis as one interconnected injury program among others.
A sepsis-induced ALI review argues lung injury may be attenuated by regulating autophagy, ferroptosis, and pyroptosis across shared nodes (including ACSL4 and GPX4-axis signaling).
- Does ICU sedative Dex blunt kidney ferroptosis after I/R?— single-agent mouse I/R study — not a sepsis ALI trial
Study Role Design N Population Outcome Which cell-death programs drive septic acute lung injury? Supports OtherNarrative mechanistic review of autophagy, ferroptosis, and pyroptosis literature in LPS/CLP sepsis-induced ALI (not a new primary experiment) No primary analytic N; synthesizes published LPS/CLP and related studies Published preclinical (and cited clinical framework) literature on sepsis-induced ALI/ARDS Mapped death-pathway mechanisms and candidate pharmacologic targets for septic lung injury Does ICU sedative Dex blunt kidney ferroptosis after I/R? Qualifiessingle-agent mouse I/R study — not a sepsis ALI trial Animal / in-vitroMouse bilateral renal I/R (45 min/48 h) plus HEK293T OGD/R with Dex and ACSL4/α2-AR manipulations Multiple animal/cell assay groups; no single primary clinical N C57BL/6 mice and HEK293T cells under renal I/R or OGD/R stress Ferroptosis, inflammation, and ACSL4 signaling after Dex via α2-AR Triggering tumor ferroptosis can help checkpoint therapy in cold tumors (preclinical).
In EGFR-mutant NSCLC models, cisplatin-driven tumor ferroptosis polarized N1 neutrophils and supported T-cell/Th1 programs that synergized with immune checkpoint inhibitor therapy.
- Does blocking IRE1/JNK calm ferroptosis in AKI?— renal protection restrains ferroptosis — opposite therapeutic direction from oncology induction
Study Role Design N Population Outcome How does cisplatin boost checkpoint therapy? Supports Animal / in-vitroTumor-cell ferroptosis, N1 neutrophil polarization, and ICI efficacy after cisplatin Preclinical tumor models and cell experiments Tumor cells and mouse tumor-microenvironment models ICI efficacy after cisplatin-induced ferroptosis and neutrophil polarization Does blocking IRE1/JNK calm ferroptosis in AKI? Qualifiesrenal protection restrains ferroptosis — opposite therapeutic direction from oncology induction Animal / in-vitroMouse renal ischemia–reperfusion plus hypoxia/reoxygenation in HK-2 cells; IRE1/JNK and ferroptosis Animal and cell experiments; no single human N Mice with renal ischemia–reperfusion injury and cultured human tubular epithelial cells Ferroptosis in acute kidney injury after IRE1/JNK pathway inhibition Blocking IRE1/JNK can attenuate ferroptosis-linked renal I/R injury in mice/cells.
Renal ischemia/reperfusion activated IRE1/JNK with ferroptotic tubular injury; inhibiting that axis improved BUN/creatinine and ferroptosis markers, aligning with ferrostatin-1-style protection.
- Does ICU sedative Dex blunt kidney ferroptosis after I/R?— another renal I/R ferroptosis-protection model — different drug/node (Dex/ACSL4 vs IRE1/JNK)
Study Role Design N Population Outcome Does blocking IRE1/JNK calm ferroptosis in AKI? Supports Animal / in-vitroMouse renal ischemia–reperfusion plus hypoxia/reoxygenation in HK-2 cells; IRE1/JNK and ferroptosis Animal and cell experiments; no single human N Mice with renal ischemia–reperfusion injury and cultured human tubular epithelial cells Ferroptosis in acute kidney injury after IRE1/JNK pathway inhibition Does ICU sedative Dex blunt kidney ferroptosis after I/R? Qualifiesanother renal I/R ferroptosis-protection model — different drug/node (Dex/ACSL4 vs IRE1/JNK) Animal / in-vitroMouse bilateral renal I/R (45 min/48 h) plus HEK293T OGD/R with Dex and ACSL4/α2-AR manipulations Multiple animal/cell assay groups; no single primary clinical N C57BL/6 mice and HEK293T cells under renal I/R or OGD/R stress Ferroptosis, inflammation, and ACSL4 signaling after Dex via α2-AR Valproic acid can restrain cisplatin-induced tubular ferroptosis in mice, unlike cisplatin’s tumor-ferroptosis story.
In cisplatin AKI mice and tubular cells, VPA (like ferrostatin-1) lowered creatinine/BUN, restored GPX4, and reduced ACSL4-linked lipid peroxidation; GPX4 siRNA wiped out VPA’s protection.
- How does cisplatin boost checkpoint therapy?— cisplatin inducing tumor ferroptosis to help ICI — opposite direction from blocking kidney ferroptosis after cisplatin
- Does ICU sedative Dex blunt kidney ferroptosis after I/R?— Dex renal I/R protection — different insult and drug than cisplatin+VPA
Study Role Design N Population Outcome Can an epilepsy drug stop cisplatin kidney ferroptosis? Supports Animal / in-vitroCisplatin AKI in C57BL/6 mice (5 groups, n=5) plus HK-2 cells and 3 human AKI biopsies vs 3 tumor-adjacent controls; VPA vs ferrostatin-1 N=25 · 25 mice (5 per group); human histology n=3 AKI + 3 controls; in vitro HK-2 with VPA/Fer-1 and GPX4 siRNA Male C57BL/6 mice with cisplatin AKI, HK-2 tubular cells, and human AKI biopsy vs renal-cancer adjacent tissue Kidney function (creatinine, BUN), histology, lipid peroxidation, ACSL4/GPX4, and rescue by VPA or Fer-1 How does cisplatin boost checkpoint therapy? Qualifiescisplatin inducing tumor ferroptosis to help ICI — opposite direction from blocking kidney ferroptosis after cisplatin Animal / in-vitroTumor-cell ferroptosis, N1 neutrophil polarization, and ICI efficacy after cisplatin Preclinical tumor models and cell experiments Tumor cells and mouse tumor-microenvironment models ICI efficacy after cisplatin-induced ferroptosis and neutrophil polarization Does ICU sedative Dex blunt kidney ferroptosis after I/R? QualifiesDex renal I/R protection — different insult and drug than cisplatin+VPA Animal / in-vitroMouse bilateral renal I/R (45 min/48 h) plus HEK293T OGD/R with Dex and ACSL4/α2-AR manipulations Multiple animal/cell assay groups; no single primary clinical N C57BL/6 mice and HEK293T cells under renal I/R or OGD/R stress Ferroptosis, inflammation, and ACSL4 signaling after Dex via α2-AR
Debates
Tensions and limits
Some items are genuine disagreements on the same question. Others mark different assays, populations, or outcomes.
A mouse renal I/R pharmacologic result and a sepsis ALI pathway review do not establish how much ferroptosis dominates human critical illness versus apoptosis/pyroptosis.
A mouse renal I/R pharmacologic result and a sepsis ALI pathway review do not establish how much ferroptosis dominates human critical illness versus apoptosis/pyroptosis.
- Does ICU sedative Dex blunt kidney ferroptosis after I/R?
- Which cell-death programs drive septic acute lung injury?
Study Role Design N Population Outcome Does ICU sedative Dex blunt kidney ferroptosis after I/R? Supports Animal / in-vitroMouse bilateral renal I/R (45 min/48 h) plus HEK293T OGD/R with Dex and ACSL4/α2-AR manipulations Multiple animal/cell assay groups; no single primary clinical N C57BL/6 mice and HEK293T cells under renal I/R or OGD/R stress Scr/BUN and ferroptosis/ACSL4 readouts after renal I/R Which cell-death programs drive septic acute lung injury? Supports OtherNarrative mechanistic review of autophagy, ferroptosis, and pyroptosis literature in LPS/CLP sepsis-induced ALI (not a new primary experiment) No primary analytic N; synthesizes published LPS/CLP and related studies Published preclinical (and cited clinical framework) literature on sepsis-induced ALI/ARDS Narrative map of cell-death pathways in sepsis ALI
PaperFren reads this as a limit on how far one study travels — different assays, populations, or outcomes — not a forced fight between papers.
Cisplatin-induced ferroptosis aided ICI efficacy in cold tumors vs IRE1/JNK blockade reduced ferroptosis-linked kidney I/R injury
Cisplatin-induced ferroptosis aided ICI efficacy in cold tumors vs IRE1/JNK blockade reduced ferroptosis-linked kidney I/R injury
Study Role Design N Population Outcome How does cisplatin boost checkpoint therapy? Supports Animal / in-vitroTumor-cell ferroptosis, N1 neutrophil polarization, and ICI efficacy after cisplatin Preclinical tumor models and cell experiments Tumor cells and mouse tumor-microenvironment models ICI efficacy after cisplatin-induced ferroptosis and neutrophil polarization Does blocking IRE1/JNK calm ferroptosis in AKI? Supports Animal / in-vitroMouse renal ischemia–reperfusion plus hypoxia/reoxygenation in HK-2 cells; IRE1/JNK and ferroptosis Animal and cell experiments; no single human N Mice with renal ischemia–reperfusion injury and cultured human tubular epithelial cells Ferroptosis in acute kidney injury after IRE1/JNK pathway inhibition
Qualified studies asking the same question reach different answers. The disagreement is listed, not scored.
Cisplatin can be used to induce tumor ferroptosis in oncology models and also drives kidney ferroptosis that VPA tries to block. Same molecule, opposite therapeutic aims.
Cisplatin can be used to induce tumor ferroptosis in oncology models and also drives kidney ferroptosis that VPA tries to block. Same molecule, opposite therapeutic aims.
Study Role Design N Population Outcome How does cisplatin boost checkpoint therapy? Supports Animal / in-vitroTumor-cell ferroptosis, N1 neutrophil polarization, and ICI efficacy after cisplatin Preclinical tumor models and cell experiments Tumor cells and mouse tumor-microenvironment models ICI efficacy after cisplatin-induced ferroptosis and neutrophil polarization Can an epilepsy drug stop cisplatin kidney ferroptosis? Supports Animal / in-vitroCisplatin AKI in C57BL/6 mice (5 groups, n=5) plus HK-2 cells and 3 human AKI biopsies vs 3 tumor-adjacent controls; VPA vs ferrostatin-1 N=25 · 25 mice (5 per group); human histology n=3 AKI + 3 controls; in vitro HK-2 with VPA/Fer-1 and GPX4 siRNA Male C57BL/6 mice with cisplatin AKI, HK-2 tubular cells, and human AKI biopsy vs renal-cancer adjacent tissue Kidney function (creatinine, BUN), histology, lipid peroxidation, ACSL4/GPX4, and rescue by VPA or Fer-1
PaperFren reads this as a limit on how far one study travels — different assays, populations, or outcomes — not a forced fight between papers.
Timeline
How understanding moved
Study years are when the paper was published. Evidence edits are dated changes to this page's claims. Explanations are when PaperFren added a Discovery — not a claim that the science happened that day.
2026
Concept page published
Ferroptosis
- Added a scope qualifier
Does blocking IRE1/JNK calm ferroptosis in AKI?
- Added a scope qualifier
Does ICU sedative Dex blunt kidney ferroptosis after I/R?
- Added a supporting study
How does cisplatin boost checkpoint therapy?
- Added a supporting study
Does blocking IRE1/JNK calm ferroptosis in AKI?
Concept page published
Ferroptosis
New claim
In EGFR-mutant NSCLC models, cisplatin-driven tumor ferroptosis polarized N1 neutrophils and supported T-cell/Th1 programs that synergized with immune checkpoint inhibitor therapy.
New claim
Renal ischemia/reperfusion activated IRE1/JNK with ferroptotic tubular injury; inhibiting that axis improved BUN/creatinine and ferroptosis markers, aligning with ferrostatin-1-style protection.
New tension
- Added a scope qualifier
How does cisplatin boost checkpoint therapy?
- Added a scope qualifier
Does ICU sedative Dex blunt kidney ferroptosis after I/R?
- Added a supporting study
Can an epilepsy drug stop cisplatin kidney ferroptosis?
- Added a supporting study
How does cisplatin boost checkpoint therapy?
- Added a supporting study
Can an epilepsy drug stop cisplatin kidney ferroptosis?
New claim
In cisplatin AKI mice and tubular cells, VPA (like ferrostatin-1) lowered creatinine/BUN, restored GPX4, and reduced ACSL4-linked lipid peroxidation; GPX4 siRNA wiped out VPA’s protection.
New tension
Cisplatin can be used to induce tumor ferroptosis in oncology models and also drives kidney ferroptosis that VPA tries to block. Same molecule, opposite therapeutic aims.
Change log
What changed
Dated edits to this page's evidence: studies added or removed from a claim, claims added or withdrawn, and new explanations tagged here. Coverage edits are distinct from reviewed research changes and corrections. Dates record PaperFren updates; study publication dates appear in the timeline.
In cisplatin AKI mice and tubular cells, VPA (like ferrostatin-1) lowered creatinine/BUN, restored GPX4, and reduced ACSL4-linked lipid peroxidation; GPX4 siRNA wiped out VPA’s protection.
- Coverage updated · New claim
- Coverage updated · Added a supporting study: Can an epilepsy drug stop cisplatin kidney ferroptosis?
- Coverage updated · Added a scope qualifier: How does cisplatin boost checkpoint therapy?
- Coverage updated · Added a scope qualifier: Does ICU sedative Dex blunt kidney ferroptosis after I/R?
Cisplatin can be used to induce tumor ferroptosis in oncology models and also drives kidney ferroptosis that VPA tries to block. Same molecule, opposite therapeutic aims.
- Coverage updated · New tension
- Coverage updated · Added a supporting study: How does cisplatin boost checkpoint therapy?
- Coverage updated · Added a supporting study: Can an epilepsy drug stop cisplatin kidney ferroptosis?
- Coverage updated · Concept page published
In EGFR-mutant NSCLC models, cisplatin-driven tumor ferroptosis polarized N1 neutrophils and supported T-cell/Th1 programs that synergized with immune checkpoint inhibitor therapy.
- Coverage updated · New claim
- Coverage updated · Added a supporting study: How does cisplatin boost checkpoint therapy?
- Coverage updated · Added a scope qualifier: Does blocking IRE1/JNK calm ferroptosis in AKI?
Renal ischemia/reperfusion activated IRE1/JNK with ferroptotic tubular injury; inhibiting that axis improved BUN/creatinine and ferroptosis markers, aligning with ferrostatin-1-style protection.
- Coverage updated · New claim
- Coverage updated · Added a supporting study: Does blocking IRE1/JNK calm ferroptosis in AKI?
- Coverage updated · Added a scope qualifier: Does ICU sedative Dex blunt kidney ferroptosis after I/R?
- Coverage updated · New tension
- Coverage updated · Concept page published
Papers
5 studies in this library bear on Ferroptosis, ordered by citations.
- Does ICU sedative Dex blunt kidney ferroptosis after I/R?
In mice and kidney cells, dexmedetomidine lessened ferroptosis-linked renal I/R injury by restraining ACSL4 through α2-AR.
- How does cisplatin boost checkpoint therapy?
Cisplatin-triggered tumor ferroptosis polarized N1 neutrophils and remodeled cold NSCLC tumors toward hotter T-cell/Th1 states, synergizing with ferroptosis activators in EGFR-mutant settings.
- Does blocking IRE1/JNK calm ferroptosis in AKI?
In I/R mice and H/R HK-2 cells, IRE1/JNK activation tracked with ferroptosis; inhibiting the pathway improved BUN/creatinine and ferroptosis markers.
- Which cell-death programs drive septic acute lung injury?
This review maps how unbalanced autophagy, ferroptosis, and pyroptosis worsen sepsis-induced ALI and which drugs might retune them.
- Can an epilepsy drug stop cisplatin kidney ferroptosis?
Valproic acid, like ferrostatin-1, improved cisplatin AKI in mice by reversing GPX4 loss and ACSL4-linked lipid peroxidation; GPX4 siRNA wiped out VPA’s protection in tubular cells.
Compare studies
Select 2–10 studies. Design and N are labels, not a ranking.
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Questions
What is still open
A mouse renal I/R pharmacologic result and a sepsis ALI pathway review do not establish how much ferroptosis dominates human critical illness versus apoptosis/pyroptosis.
Cisplatin-induced ferroptosis aided ICI efficacy in cold tumors vs IRE1/JNK blockade reduced ferroptosis-linked kidney I/R injury
Cisplatin can be used to induce tumor ferroptosis in oncology models and also drives kidney ferroptosis that VPA tries to block. Same molecule, opposite therapeutic aims.
Ask PaperFren about Ferroptosis
Study this conceptflashcards and short-answer questions
Name two ferroptosis-related nodes often paired in pathway maps.
ACSL4 and GPX4 (Xc–GSH–GPX4 axis).
Why can oncology and critical care ‘want’ opposite ferroptosis directions?
Cancer therapy may want to trigger it; organ protection may want to restrain it.
Give one oncology vs one organ-injury ferroptosis goal from this library.
Induce ferroptosis to aid ICI (cisplatin/N1 neutrophil models); restrain ferroptosis in renal I/R (IRE1/JNK or Dex/ACSL4 models).
How can cisplatin both ‘cause’ and ‘treat via’ ferroptosis without contradiction?
Oncology papers induce ferroptosis in tumors; the VPA paper blocks ferroptosis in kidney tubules after cisplatin nephrotoxicity. Tissue and intent differ.