SIH is a lipophilic cell-permeable iron chelator.1,2 It stimulates iron release from, and inhibits iron uptake by, SK-N-MC human neuroblastoma cells when used at a concentration of 25 µM.3 SIH inhibits cumene hydroperoxide-induced membrane lipid peroxidation but not ABAP-induced formation of cytosolic peroxyl radicals in HepG2 human hepatocellular carcinoma cells (IC50s = 0.833 and >4,000 µM, respectively).1 It inhibits hydrogen peroxide-induced mitochondrial membrane depolarization in H9c2 rat cardiomyocytes (EC50 = 0.8 µM).2 SIH (1.0 mg/kg) completely prevents mortality in a rabbit model of cardiotoxicity induced by chronic administration of daunorubicin .4
1.Hofer, T., JØrgensen, T.Ø., and Olsen, R.L.Comparison of food antioxidants and iron chelators in two cellular free radical assays: Strong protection by luteolinJ. Agric. Food Chem.62(33)8402-8410(2014) 2.šim?nek, T., Boer, C., Bouwman, R.A., et al.SIH—a novel lipophilic iron chelator—protects H9c2 cardiomyoblasts from oxidative stress-induced mitochondrial injury and cell deathJ. Mol. Cell. Cardiol.39(2)345-354(2005) 3.Wu, Z., Palanimuthu, D., Braidy, N., et al.Novel multifunctional iron chelators of the aroyl nicotinoyl hydrazone class that markedly enhance cellular NAD+ /NADH ratiosBr. J. Pharmacol.177(9)1967-1987(2019) 4.št?rba, M., PopelovÁ, O., šim?nek, T., et al.Iron chelation-afforded cardioprotection against chronic anthracycline cardiotoxicity: A study of salicylaldehyde isonicotinoyl hydrazone (SIH)Toxicology235(3)150-166(2007)