PMID- 34410949
OWN - NLM
STAT- MEDLINE
DCOM- 20210823
LR  - 20210915
IS  - 1791-7549 (Electronic)
IS  - 0258-851X (Print)
IS  - 0258-851X (Linking)
VI  - 35
IP  - 5
DP  - 2021 Sep-Oct
TI  - In Vitro Toxicological Assessment of Gadodiamide in Normal Brain SVG P12 Cells.
PG  - 2621-2630
LID - 10.21873/invivo.12544 [doi]
AB  - BACKGROUND/AIM: Magnetic resonance imaging (MRI) is a technique for evaluating 
      patients with primary and metastatic tumors. The contrast agents improve the 
      diagnostic accuracy of MRI. Large quantities of a contrast agent must be 
      administrated into the patient to obtain useful images, which leads to cell 
      injury. Gadolinium has been reported to cause central lobular necrosis of the 
      liver and nephrogenic systemic fibrosis. However, the toxicity caused on brain 
      tissue is uncertain. MATERIALS AND METHODS: This study mainly aimed on the in 
      vitro study of high concentration (2 and 5-fold of normal concentration) 
      gadolinium-based contrast agents (GBCAs), gadodiamide (Omniscan((R))), on normal 
      brain glial SVG P12 cells. MTT assay, DAPI staining, immunofluorescent staining, 
      LysoTracker Red staining, and western blotting analysis were applied on the 
      cells. RESULTS: The viability of gadodiamide (1.3, 2.6, 5.2, 13 and 26 
      mM)-treated SVG P12 cells was significantly reduced after 24 h of incubation. 
      Gadodiamide caused significant autophagic flux at 2.6, 5.2 and 13.0 mM as seen by 
      acridine orange (AO) staining, LC-3-GFP and LysoTracker Red staining. The 
      expression levels of autophagy-related proteins such as beclin-1, ATG-5, ATG-14 
      and LC-3 II were up-regulated after 24 h of gadodiamide incubation. Autophagy 
      inhibitors including 3-methyladenine (3-MA), chloroquine (CQ) and bafilomycin A1 
      (Baf) significantly alleviated the autophagic cell death effect of gadodiamide on 
      normal brain glial SVG P12 cells. Gadodiamide induced significant apoptotic 
      effects at 5.2 mM and 13.0 mM as seen by DAPI staining and the pan-caspase 
      inhibitor significantly alleviated the apoptotic effect. Gadodiamide at 5.2 mM 
      and 13.0 mM inhibited antiapoptotic protein expression levels of Bcl-2 and 
      Bcl-XL, while promoted pro-apoptotic protein expression levels of Bax, BAD, 
      cytochrome c, Apaf-1, cleaved-caspase-9 and cleaved-caspase-3. CONCLUSION: Normal 
      brain glial SVG P12 cells treated with high concentrations of gadodiamide can 
      undergo autophagy and apoptosis.
CI  - Copyright (c) 2021 International Institute of Anticancer Research (Dr. George J. 
      Delinasios), All rights reserved.
FAU - Tsai, Yuh-Feng
AU  - Tsai YF
AD  - Department of Diagnostic Radiology, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, 
      Taiwan, R.O.C.
AD  - School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan, R.O.C.
FAU - Yang, Jai-Sing
AU  - Yang JS
AD  - Department of Medical Research, China Medical University Hospital, China Medical 
      University, Taichung, Taiwan, R.O.C.
FAU - Tsai, Fuu-Jen
AU  - Tsai FJ
AD  - School of Chinese Medicine, College of Chinese Medicine, China Medical 
      University, Taichung, Taiwan, R.O.C.
AD  - China Medical University Children's Hospital, China Medical University, Taichung, 
      Taiwan, R.O.C.
FAU - Lu, Chi-Cheng
AU  - Lu CC
AD  - Department of Sport Performance, National Taiwan University of Sport, Taichung, 
      Taiwan, R.O.C.
FAU - Chiu, Yu-Jen
AU  - Chiu YJ
AD  - Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei 
      Veterans General Hospital, Taipei, Taiwan, R.O.C.; chiou70202@gmail.com 
      sctsai@mail.cmu.edu.tw.
AD  - Department of Surgery, School of Medicine, National Yang Ming Chiao Tung 
      University, Taipei, Taiwan, R.O.C.
AD  - Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, 
      Taiwan, R.O.C.
FAU - Tsai, Shih-Chang
AU  - Tsai SC
AD  - Department of Biological Science and Technology, China Medical University, 
      Taichung, Taiwan, R.O.C. chiou70202@gmail.com sctsai@mail.cmu.edu.tw.
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - In Vivo
JT  - In vivo (Athens, Greece)
JID - 8806809
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 84F6U3J2R6 (gadodiamide)
RN  - K2I13DR72L (Gadolinium DTPA)
SB  - IM
MH  - Apoptosis
MH  - *Apoptosis Regulatory Proteins/metabolism
MH  - Brain/metabolism
MH  - *Gadolinium DTPA/toxicity
MH  - Humans
PMC - PMC8408707
OTO - NOTNLM
OT  - Brain glial SVG P12 cells
OT  - apoptosis
OT  - autophagy
OT  - gadodiamide
COIS- The Authors declare no conflicts of interest in relation to this study.
EDAT- 2021/08/20 06:00
MHDA- 2021/08/24 06:00
PMCR- 2021/09/03
CRDT- 2021/08/19 17:23
PHST- 2021/05/01 00:00 [received]
PHST- 2021/05/15 00:00 [revised]
PHST- 2021/06/01 00:00 [accepted]
PHST- 2021/08/19 17:23 [entrez]
PHST- 2021/08/20 06:00 [pubmed]
PHST- 2021/08/24 06:00 [medline]
PHST- 2021/09/03 00:00 [pmc-release]
AID - 35/5/2621 [pii]
AID - 10.21873/invivo.12544 [doi]
PST - ppublish
SO  - In Vivo. 2021 Sep-Oct;35(5):2621-2630. doi: 10.21873/invivo.12544.