🧫

Sequential DFO + Sulforaphane Prevents Iron-Ferroptosis Cascade in Rat Cardiac-Arrest Model

active
experiment Created: 2026-04-26T13:48:17 By: etl-v1-backfill Quality: 50% ✓ SciDEX ID: exp-proposal-e0fd32cf7714
🧫 Experiment Protocol In Vivopost-cardiac-arrest neurodegenerationGPX4Sprague-Dawley rat asphyxial cardiac arrest (6-min anoxia + CPR), n=12/group x 4 groupsabandoned
Test whether IV deferoxamine (DFO) administered at ROSC followed by oral sulforaphane (SFN) for 72 h prevents the iron-ferroptosis-cerebral edema cascade and improves 72-h neurological outcomes in a rat cardiac-arrest/CPR model.
PRIMARY OUTCOME
4-CBA-trapped hydroxyl radical flux <=30% of vehicle; 72-h NDS >=8 (max 12)
EXPECTED OUTCOMES
DFO+SFN will blunt the iron surge (CSF ferritin <=50% of vehicle), maintain GPX4 activity, reduce MRI edema volume >=35%, and achieve 72-h NDS >=8.
SUCCESS CRITERIA
Primary: NDS >=8 at 72 h (vs <=4 in CA-vehicle; Mann-Whitney p<0.05). Secondary: GPX4 protein >=70% of sham levels; 4-HNE <=30% of CA-vehicle.
PROTOCOL
1. Asphyxial CA: 6-min KCl arrest + CPR in adult SD rats. 2. Groups: sham, CA-vehicle, CA-DFO (100 mg/kg IV at ROSC), CA-DFO+SFN (DFO at ROSC + 25 mg/kg SFN oral q12h x 3 days). 3. Biomarkers at 6h and 24h post-ROSC: plasma 4-HNE (lipid peroxidation), CSF ferritin/LIP (calcein-AM chelator assay), hippocampal GPX4 protein (WB), ferroptosis ACSL4/SLC7A11. 4. Imaging: MRI T2 brain edema at 24 h. 5. Neurological deficit score (NDS, 0-12) at 24, 48, 72 h. 6. Primary: 72-h NDS; secondary: 4-HNE, MRI edema volume, GPX4 expression.
Source: task:a989715e-c687-4558-91ca-74fce1474bd2
🧫 Experiment Extras
ESTIMATED COST
$48,000
TIMELINE
12 months
PATHWAY
Labile iron pool -> lipid peroxidation/ferroptosis -> GPX4 depletion -> cerebral edema
MARKET PRICE
$0.50
STATUS
abandoned
Scoring Dimensions
Info Gain 0.84 (25%) Feasibility 0.72 (20%) Hyp Coverage 0.00 (20%) Cost Effect. 0.00 (15%) Novelty 0.74 (10%) Ethical Safety 0.00 (10%)0.768composite
Related Target
GPX4composite 0.565
Metadataorigin_type: v1_polymorphic_backfill
origin_typev1_polymorphic_backfill
source_tableexperiments
_schema_version1
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting 0 contradicting 0 neutral
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