Yuh-Feng Tsai1,2, Jai-Sing Yang3, Yu-Jen Chiu4,5,6, Chia-Wen Tsai7,8, DA-Tian Bau9,8,10, Wen-Shin Chang9,8. 1. Department of Diagnostic Radiology, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, R.O.C. 2. School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan, R.O.C. 3. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C. 4. Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C. 5. Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, R.O.C. 6. Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, R.O.C. 7. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C. 8. Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C. 9. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C.; artbau2@gmail.com. 10. Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan, R.O.C.
Abstract
BACKGROUND/AIM: Gadolinium has been reported to cause liver lobular necrosis and nephrogenic systemic fibrosis. However, its toxicity to the skin remains unknown. This study aimed to investigate the effect of a high dose of gadolinium-based contrast agent gadodiamide on the human keratinocyte HaCaT cell line. MATERIALS AND METHODS: Cell viability was assessed using MTT assay, and autophagy was assessed using acridine orange and LysoTracker Red staining. Western blotting was performed to verify the changes in Bcl2 and Bax levels. RESULTS: The viability of HaCaT cells was significantly suppressed after gadodiamide treatment. Interestingly, gadodiamide caused autophagic vacuoles, whereas the autophagy inhibitors 3-methyladenine and chloroquine significantly alleviated autophagic cell death. Simultaneously, gadodiamide induced apoptosis, which was reduced by caspase inhibitors. Gadodiamide also inhibited Bcl-2 expression and promoted Bax expression. CONCLUSION: Gadodiamide induced both autophagy and apoptosis in HaCaT cells. Physicians should carefully assess the gadodiamide dosage used clinically.
BACKGROUND/AIM: Gadolinium has been reported to cause liver lobular necrosis and nephrogenic systemic fibrosis. However, its toxicity to the skin remains unknown. This study aimed to investigate the effect of a high dose of gadolinium-based contrast agent gadodiamide on the human keratinocyte HaCaT cell line. MATERIALS AND METHODS: Cell viability was assessed using MTT assay, and autophagy was assessed using acridine orange and LysoTracker Red staining. Western blotting was performed to verify the changes in Bcl2 and Bax levels. RESULTS: The viability of HaCaT cells was significantly suppressed after gadodiamide treatment. Interestingly, gadodiamide caused autophagic vacuoles, whereas the autophagy inhibitors 3-methyladenine and chloroquine significantly alleviated autophagic cell death. Simultaneously, gadodiamide induced apoptosis, which was reduced by caspase inhibitors. Gadodiamide also inhibited Bcl-2 expression and promoted Bax expression. CONCLUSION: Gadodiamide induced both autophagy and apoptosis in HaCaT cells. Physicians should carefully assess the gadodiamide dosage used clinically.
Authors: Ferenc Czeyda-Pommersheim; Diego R Martin; James R Costello; Bobby Kalb Journal: Magn Reson Imaging Clin N Am Date: 2017-11 Impact factor: 2.266