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.
Carboxy-PTIO potassium salt是一种一氧化氮(NO)清除剂[1]。Carboxy-PTIO potassium salt可与NO发生化学计量反应,可用于NO的EPR检测[2]。
在体外,Carboxy-PTIO potassium salt(200µM)预处理A375-S2细胞1h,显著抑制physalin A刺激的NO表达,减少procaspase-3和PARP裂解,逆转mTOR和p-mTOR水平降低,还抑制细胞中的LC3 I向LC3 II转化[3]。Carboxy-PTIO potassium salt(100µM)预处理HUVEC细胞6h,显著增强了IL-1β对PGIS的抑制作用[4]。Carboxy-PTIO potassium salt(0.5µM,1µM)预处理MDA-MB-231细胞1h,显著降低了化合物3a-f对细胞的抑制活性[5]。
在体内,Carboxy-PTIO potassium salt(0.3-1.2 mg/kg)静脉注射治疗脑缺血性损伤小鼠,即使治疗延迟长达4小时,脑梗塞的发生率也呈剂量依赖性减少,降低了27-30% [6]。Carboxy-PTIO potassium salt(0.056-1.70mg/kg/min)通过静脉注射持续60min治疗内毒素休克大鼠,明显改善了大鼠低血压、肾功能不全症状,并且避免了休克状态[7]。