Dexamethasone Sodium Phosphate is a glucocorticoid and an interleukin receptor inhibitor. The IC50 value for inhibiting cyclooxygenase-2 (COX-2) is 7.3μM [1-2]. COX is an enzyme in the prostaglandin-prostaglandin-prostanoid pathway, and the expression of COX-2 can be induced by inflammatory stimuli or mutagens, inflammatory cytokines, and transcription factor CCAAT enhancer binding protein (c/EBP) β [3]. Dexamethasone Sodium Phosphate has been used to treat various inflammatory diseases, arthritis, and endocrine disorders [4].
In vitro, in the presence of cytokines and basic fibroblast growth factor (bFGF), Dexamethasone Sodium Phosphate (1-1000nM; 24h) can increase DNA synthesis in airway smooth muscle cells (ASM) in a concentration-dependent manner [5]. Dexamethasone Sodium Phosphate (0.1-100μM; 24h) treatment of human lens epithelial cells (HLEC) promotes HLEC cell proliferation at a concentration of 0.1μM, while at concentrations of 1-100μM, it increases cell apoptosis in a dose-dependent manner [6].
In vivo, oral administration of Dexamethasone Sodium Phosphate (0.075 and 0.15mg/kg/day; 4 weeks;) can significantly improve the rigidity state of Parkinsonian rats in a concentration-dependent manner [7]. Dexamethasone Sodium Phosphate (5 and 10mg/kg/day; 7 days; i.p.) treatment of mice with acute lung injury (ALI) induced by lipopolysaccharide (LPS) significantly reduces the expression of COX-2, iNOS, and NF-κB p65 in mice, lowers the levels of malondialdehyde (MDA) and myeloperoxidase (MPO) activity, increases the content of glutathione (GSH), and has an effective anti-inflammatory effect [8].
References:
[1] Hui, B., Yao, X., Zhang, L., et al. Naunyn Schmiedebergs Arch. Pharmacol. 393(9), 1761-1768 (2020) .
[2] Blanco FJ, Guitian R, Moreno J, de Toro FJ, Galdo F. Effect of antiinflammatory drugs on COX-1 and COX-2 activity in human articular chondrocytes. J Rheumatol. 1999;26(6):1366-1373.
[3] Ristimäki A, Narko K, Hla T. Down-regulation of cytokine-induced cyclo-oxygenase-2 transcript isoforms by dexamethasone: evidence for post-transcriptional regulation[J]. Biochemical Journal, 1996, 318(1): 325-331.
[4] Tsao P W, Suzuki T, Totsuka R, et al. The effect of dexamethasone on the expression of activated NF-κB in adjuvant arthritis[J]. Clinical immunology and immunopathology, 1997, 83(2): 173-178.
[5] Vlahos R, Stewart AG. Interleukin-1alpha and tumour necrosis factor-alpha modulate airway smooth muscle DNA synthesis by induction of cyclo-oxygenase-2: inhibition by dexamethasone and fluticasone propionate. Br J Pharmacol. 1999;126(6):1315-1324.
[6] Petersen A, Carlsson T, Karlsson J O, et al. Effects of dexamethasone on human lens epithelial cells in culture[J]. Molecular vision, 2008, 14: 1344.
[7] Ardestani M S, Mehrab H, Sadeghzadeh N. Effects of dexamethasone and betamethasone as COX-2 gene expression inhibitors on rigidity in a rat model of Parkinson′ s disease[J]. Indian Journal of Pharmacology, 2007, 39(5): 235-239.
[8] Al-Harbi N O, Imam F, Al-Harbi M M, et al. Dexamethasone attenuates LPS-induced acute lung injury through inhibition of NF-κB, COX-2, and pro-inflammatory mediators[J]. Immunological Investigations, 2016, 45(4): 349-369.
Dexamethasone Sodium Phosphate是一种糖皮质激素，也是白细胞介素受体抑制剂，抑制环氧化酶-2（COX-2）的IC50值为7.3μM [1-2]。COX是前列腺素-前列环素-血栓素途径中的一种酶，COX-2的表达可以通过炎症刺激或诱变剂、炎症性细胞因子和转录因子CCAAT增强子结合蛋白（c/EBP）β诱导 [3]。Dexamethasone Sodium Phosphate已被用于治疗各种炎症性疾病、关节炎和内分泌紊乱 [4]。
在体外，在细胞因子和碱性成纤维细胞生长因子（bFGF）存在下，Dexamethasone Sodium Phosphate（1-1000nM; 24h）能够以浓度依赖性方式增加人气道平滑肌细胞（ASM）的DNA合成 [5]。Dexamethasone Sodium Phosphate（0.1-100μM; 24h）处理人晶状体上皮细胞（HLEC），在0.1μM浓度下促进HLEC细胞增殖，而在1-100μM浓度下以剂量依赖性方式增加了细胞凋亡 [6]。
在体内，Dexamethasone Sodium Phosphate（0.075和0.15mg/kg/day; 4 weeks; ）口服治疗能够以浓度依赖性方式显著改善帕金森大鼠的强直状态 [7]。Dexamethasone Sodium Phosphate（5和10mg/kg/day;7 days; i.p.）治疗脂多糖（LPS）诱导的急性肺损伤（ALI）小鼠，显著降低了小鼠COX-2、iNOS和NF-κB p65的表达，降低丙二醛（MDA）水平和髓过氧化物酶（MPO）活性，增加了谷胱甘肽（GSH）含量，具有有效的抗炎作用 [8]。