Iodixanol

Iodixanol is a non-ionic, dimeric, iso-osmolar iodinated X-ray contrast agent. Iodixanol can absorb X-rays through the iodine atoms contained in its molecules, thereby creating artificial contrast with surrounding tissues to clearly visualize vascular and visceral structures. Iodixanol reduces adverse reactions such as endothelial damage and nephrotoxicity by maintaining an osmotic pressure equal to that of plasma. Iodixanol can be used in research related to medical imaging modalities such as cardiovascular angiography, cerebrovascular angiography, and CT enhancement^[1-4].

In vitro, LLC-PK1 cells (proximal tubular epithelial cells of porcine origin) were treated with Iodixanol (18.75–75mg I/mL) for 1 to 24 hours. Iodixanol significantly induced apoptosis and anti-proliferative effects without causing cellular necrosis^[5]. Human LAD2 mast cells were treated with Iodixanol (4–30%vol) for 30 minutes. Iodixanol significantly induced the release of β-hexosaminidase and histamine, promoted intracellular calcium mobilization, and facilitated the synthesis of inflammatory cytokines by activating PLC-γ- and PI3K-related pathways, thereby exacerbating pseudo-allergic reactions^[6].

In vivo, C57BL/6J mice were pretreated with dehydration and furosemide, followed by intraperitoneal injection of Iodixanol (15g I/kg; single dose). Iodixanol significantly induced mitochondrial fragmentation, dysfunction, and apoptosis in renal tubular cells, increased the levels of superoxide and malondialdehyde in renal tubules, and led to renal tubular epithelial cell damage and renal dysfunction^[7]. Normal female C57/BL6 mice were injected with Iodixanol (10g I/kg; single dose) via the tail vein. Iodixanol significantly elevated serum levels of creatinine, NGAL, and KIM-1, resulting in renal dysfunction and histological damage^[8].

References:
[1] Liu ZZ, Viegas VU, Perlewitz A, et al. Iodinated contrast media differentially affect afferent and efferent arteriolar tone and reactivity in mice: a possible explanation for reduced glomerular filtration rate. Radiology. 2012 Dec;265(3):762-71.
[2] Jensen H, Doughty RW, Grant D, et al. The effects of the iodinated X-ray contrast media iodixanol, iohexol, iopromide, and ioversol on the rat kidney epithelial cell line NRK 52-E. Ren Fail. 2011;33(4):426-33.
[3] Zhang J, Jiang Y, Rui Q, et al. Iodixanol versus iopromide in patients with renal insufficiency undergoing coronary angiography with or without PCI. Medicine (Baltimore). 2018 May;97(18):e0617.
[4] Spencer CM, Goa KL. Iodixanol. A review of its pharmacodynamic and pharmacokinetic properties and diagnostic use as an x-ray contrast medium. Drugs. 1996 Dec;52(6):899-927.
[5] Heinrich MC, Scheer M, Heckmann M, et al. Iodixanol induces apoptotic and antiproliferative effects but no necrotic cell death in renal proximal tubular cells in vitro. Rofo. 2009 Apr;181(4):349-54.
[6] Zou W, Yang S, Chen L, et al. Iodixanol activation of mast cells: Implications in the pathogenesis of iodixanol-induced delayed cutaneous adverse reactions. Toxicology. 2022 Jan 15;465:153034.
[7] Ran F, Yang Y, Yang L, et al. Capsaicin Prevents Contrast-Associated Acute Kidney Injury through Activation of Nrf2 in Mice. Oxid Med Cell Longev. 2022 May 16;2022:1763922.
[8] Kim BW, Kim HJ, Kim SH, et al. 15-Hydroxyprostaglandin dehydrogenase inhibitor prevents contrast-induced acute kidney injury. Ren Fail. 2021 Dec;43(1):168-179.

Iodixanol是一种非离子型、二聚体的等渗性碘化X线造影剂。Iodixanol 可通过其分子中含有的碘原子吸收X射线，从而在与周围组织间形成人工对比度以清晰显示血管及内脏结构，同时通过维持与血浆相等的渗透压以减少内皮损伤和肾毒性等不良反应。Iodixanol 可用于心血管造影、脑血管造影、CT增强等医学影像学的相关研究^[1-4]。

在体外，Iodixanol（18.75–75mg I/ml）处理猪肾近端小管上皮细胞（LLC-PK1）1-24小时。Iodixanol显著诱导细胞凋亡和抗增殖效应，且不引起细胞坏死^[5]。Iodixanol（4–30%vol）处理人类LAD2肥大细胞30min。Iodixanol显著诱导β-己糖胺酶和组胺的释放，促进细胞内钙离子动员，并通过激活PLC-γ和PI3K相关通路以促进炎症因子的合成，同时加剧伪过敏反应^[6]。

在体内，Iodixanol（15mg/kg；单次）腹腔注射于经脱水和呋塞米预处理的C57BL/6J小鼠。Iodixanol显著诱导了肾小管细胞的线粒体断裂、功能障碍和细胞凋亡，增加了肾小管内的超氧化物和肾脏丙二醛水平，并导致肾小管上皮细胞损伤和肾功能障碍^[7]。Iodixanol（10g I/kg；单次）尾静脉注射于正常雌性C57/BL6小鼠。Iodixanol显著升高血清肌酐、NGAL和KIM-1水平，导致肾功能障碍和组织学损伤^[8]。