GSH depletion causes ferroptosis in RPE cells To evaluate the mechanism of cell death in GSH-depleted cells, we treated RPE cells with various cell death pathway inhibitors including ferroptosis inhibitors ferrostatin-1 (Fer-1, 8 M), liproxstatin-1 (Lip-1, 600 nM), iron chelator deferoxamine (DFO, 80 M), pan-caspase inhibitor z-VAD-fmk (30 M) to inhibit apoptosis, autophagy inhibitor 3-methyladenine (3-MA, 10 mM), and lysosomal inhibitor bafilomycin A1 (Baf-A1, 75 nM)
JNK:c-Jun N-terminal Kinase
28 DanboltN
Several inflammatory markers also showed decreases, including high-sensitivity C-reactive protein (20%), TNF-alpha (48%), and IL-6 (37%)
We do not have reliable dose thresholds that predict when a typical adult will produce clinically relevant TMA from L-carnitine