Carboxy-PTIO potassium salt is a nitric oxide (NO) scavenger[1]. Carboxy-PTIO potassium salt can react stoichiometrically with NO and can be used for EPR detection of NO[2].
In vitro, pretreatment of A375-S2 cells with Carboxy-PTIO potassium salt (200µM) for 1h significantly inhibited physalin A-stimulated NO expression, reduced procaspase-3 and PARP cleavage, reversed the decrease in mTOR and p-mTOR levels, and also inhibited in the cells Conversion of LC3 I to LC3 II [3]. Pretreating HUVEC cells with Carboxy-PTIO potassium salt (100µM) for 6 hours significantly enhanced the inhibitory effect of IL-1β on PGIS [4]. Carboxy-PTIO potassium salt (0.5µM, 1µM) pretreated MDA-MB-231 cells for 1 hour, which significantly reduced the inhibitory activity of compounds 3a-f on cells [5].
In vivo, intravenous injection of Carboxy-PTIO potassium salt (0.3-1.2 mg/kg) in mice with cerebral ischemic injury resulted in a dose-dependent reduction in the incidence of cerebral infarction by 27% even when treatment was delayed for up to 4 hours. -30%[6]. Carboxy-PTIO potassium salt (0.056-1.70mg/kg/min) was injected intravenously for 60 minutes to treat endotoxic shock rats, which significantly improved the symptoms of hypotension and renal insufficiency in rats and avoided the shock state [7].
References:
[1]Pfeiffer S, Leopold E, Hemmens B, et al. Interference of carboxy-PTIO with nitric oxide-and peroxynitrite-mediated reactions[J]. Free Radical Biology and Medicine, 1997, 22(5): 787-794.
[2]T Akaike, et al. Antagonistic action of imidazolineoxyl N-oxides against endothelium-derived relaxing factor/.NO through a radical reaction. Biochemistry. 1993 Jan 26;32(3):827-32.
[3] He H, Feng Y S, Zang L H, et al. Nitric oxide induces apoptosis and autophagy; autophagy down-regulates NO synthesis in physalin A-treated A375-S2 human melanoma cells[J]. Food and chemical toxicology, 2014, 71: 128-135.
[4] Camacho M, LÓpez-Belmonte J, Vila L. Rate of vasoconstrictor prostanoids released by endothelial cells depends on cyclooxygenase-2 expression and prostaglandin I synthase activity[J]. Circulation research, 1998, 83(4): 353-365.
[5] Kang F, Zhu J, Wu J, et al. O 2-3-Aminopropyl diazeniumdiolates suppress the progression of highly metastatic triple-negative breast cancer by inhibition of microvesicle formation via nitric oxide-based epigenetic regulation[J]. Chemical Science, 2018, 9(34): 6893-6898.
[6]Lee E J, Hung Y C, Chen H Y, et al. Delayed treatment with carboxy-PTIO permits a 4-h therapeutic window of opportunity and prevents against ischemia-induced energy depletion following permanent focal cerebral ischemia in mice[J]. Neurochemical research, 2009, 34: 1157-1166.
[7]Yoshida M, Akaike T, Wada Y, et al. Therapeutic effects of imidazolineoxyl N-oxide against endotoxin shock through its direct nitric oxide-scavenging activity[J]. Biochemical and biophysical research communications, 1994, 202(2): 923-930.