title: Which iodinated contrast media is the least cytotoxic to human disc cells?
abstract: BACKGROUND
  Iodinated contrast media (CM) is commonly used for various intradiscal injections such as in discography and endoscopic spinal surgery. However, CM has been shown to be toxic to renal tissue due to its ionic strength and osmolarity and as a result of iodine-induced cytotoxicity, which has raised concern over whether there are similar negative effects on disc cells.
  
  
  OBJECTIVE
  This in vitro study was designed to identify the least cytotoxic iodinated CM to the human disc cell among four different physiochemical iodinated contrast dyes.
  
  
  METHODS
  In vitro laboratory study.
  
  
  METHODS
  Intervertebral disc tissue was obtained by discectomy from a total of 10 lumbar disc patients undergoing surgery and disc cells were isolated. The human disc cells were grown in 3D alginate bead culture with 0, 0.1, 10, and 100 mg/mL CM solutions (ionic dimer, ionic monomer, non-ionic dimer, and non-ionic monomer) and mannitol as a control for 2 days. The living cells were analyzed with trypan blue staining. Fluorescence-activated cell sorting analysis was performed using Annexin V and propidium iodide (PI) and 3D alginate bead immunostaining to identify live, apoptotic, and necrotic cells.
  
  
  RESULTS
  Human disc cell death was time- and dose-dependent in response to CM and more necrosis was observed than apoptosis. In addition, non-ionic dimeric CM (iodixanol) showed the least toxic effect on human disc cells, followed by non-ionic monomeric (iopromide), ionic dimeric (ioxaglate), and ionic monomeric CM (ioxithalamate).
  
  
  CONCLUSIONS
  Contrast media is cytotoxic to human disc cells in a dose- and time-dependent manner. This in vitro study revealed that, among four different CM preparations, non-ionic dimeric CM is the least detrimental to human disc cell viability. Careful attention should be paid to the type of CM chosen for discography and endoscopic spinal surgery. It is also necessary to investigate the detrimental effects of CM on disc cells and disc degeneration in further in vivo studies.
authors: Department of Neurosurgery, Spine and Spinal Cord Institute, Yonsei University College of Medicine, 712, Eonjuro, Gangnam-gu, Seoul, South Korea.
authors: Kyung-Hyun
authors: KH
authors: Kim
authors: Department of Neurosurgery, Spine and Spinal Cord Institute, Yonsei University College of Medicine, 712, Eonjuro, Gangnam-gu, Seoul, South Korea.
authors: Jeong-Yoon
authors: JY
authors: Park
authors: Department of Neurosurgery, Spine and Spinal Cord Institute, Yonsei University College of Medicine, 712, Eonjuro, Gangnam-gu, Seoul, South Korea.
authors: Hyo-Suk
authors: HS
authors: Park
authors: Department of Neurosurgery, Spine and Spinal Cord Institute, Yonsei University College of Medicine, 712, Eonjuro, Gangnam-gu, Seoul, South Korea. Electronic address: kuhsu@yuhs.ac.
authors: Sung-Uk
authors: SU
authors: Kuh
authors: Department of Neurosurgery, Spine and Spinal Cord Institute, Yonsei University College of Medicine, 712, Eonjuro, Gangnam-gu, Seoul, South Korea.
authors: Dong-Kyu
authors: DK
authors: Chin
authors: Department of Neurosurgery, Spine and Spinal Cord Institute, Yonsei University College of Medicine, 712, Eonjuro, Gangnam-gu, Seoul, South Korea.
authors: Keun-Su
authors: KS
authors: Kim
authors: Department of Neurosurgery, Spine and Spinal Cord Institute, Yonsei University College of Medicine, 712, Eonjuro, Gangnam-gu, Seoul, South Korea.
authors: Yong-Eun
authors: YE
authors: Cho
mesh_terms: D017209:Apoptosis; D002470:Cell Survival; D002478:Cells, Cultured; D003287:Contrast Media / Q000009:adverse effects*; D005434:Flow Cytometry; D006801:Humans; D007403:Intervertebral Disc / Q000166:cytology / Q000187:drug effects*; D014283:Triiodobenzoic Acids / Q000633:toxicity
chemical_list: D003287:Contrast Media; D014283:Triiodobenzoic Acids
keywords: Contrast media; Cytotoxicity; Disc; Ionic; Nonionic; Osmolarity