Critical care
Can an epilepsy drug stop cisplatin kidney ferroptosis?
Open access · cc by · source: Europe PMC
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.
Study at a glance
- Design
- Animal / in-vitro — Cisplatin 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
- 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
- Population
- Male C57BL/6 mice with cisplatin AKI, HK-2 tubular cells, and human AKI biopsy vs renal-cancer adjacent tissue
- Outcome
- Kidney function (creatinine, BUN), histology, lipid peroxidation, ACSL4/GPX4, and rescue by VPA or Fer-1
Structured fields used in claim comparison tables when every cited study has a complete layer.
Key findings
Ferroptosis appeared in human and mouse injured tubules. VPA or Fer-1 lowered creatinine, BUN, tissue injury, cell death, lipid peroxidation, and ACSL4 while restoring GPX4. GPX4 siRNA significantly weakened VPA’s benefit after cisplatin.
Methodology
Documented ferroptosis marks in 3 human AKI biopsies, then randomized mice to sham, cisplatin 20 mg/kg, VPA, cisplatin+VPA, or cisplatin+Fer-1 (n=5 each), and tested VPA/Fer-1 and GPX4 knockdown in HK-2 cells.
Limitations
n=5 mice per arm and 3 human biopsies cannot establish VPA as clinical AKI therapy; cisplatin nephrotoxicity still affects ~30% of treated patients and this is not a human trial.
How this study connects
Role on claims
Each row is a claim on a concept or method page where this paper supports, challenges, or qualifies the statement. Roles are hand-checked — not a model guess.
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.
Evidence for the claim as stated.
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.
Evidence for the claim as stated.
Open questions
Tensions this paper is part of
From concept pages' “where studies disagree.” Disagreement means the same question; scope means different assays, populations, or outcomes.
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.
- Supports · How does cisplatin boost checkpoint therapy?
History
When this study was placed
Dated entries from the concept change log — when this paper was added or removed as support, challenge, or qualifier on a claim.
Placed as supporting evidence on Ferroptosis
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.
Placed as supporting evidence on Ferroptosis
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.
Related papers in this topic
Same topic cluster — not a recommendation engine.