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.Magnetic resonance imaging (MRI) is a contemporary technology that produces three-dimensional images of the anatomical human body and helps in the detection and diagnosis of diseases. The density of contrast agents produces a strong contrast effect; however, patients with severe renal failure may be at risk of a serious illness called nephrogenic systemic fibrosis (NSF) that may be linked to the use of certain gadolinium-based contrast agents (GBCAs) such as gadodiamide (1, 2). GBCAs agents can be applied to the human body, providing anatomical imaging of the head, spinal cord, and vascular artery for doctors to determine the condition of the entire body (3). However, its toxicity to normal skin cells is critical, but has never been investigated.NSF is a serious, late adverse reaction to gadodiamide (4, 5). Thus, the Taiwan Food and Drug Administration suggests the use of the lowest effective dose to prevent possible adverse effects on any part of the human body (6, 7). Longterm ionized gadolinium accumulation may cause fibrosis in various tissues of the human body, including the skin. Early alterations and symptoms of NSF may include pain, itching, swelling, and erythema, which usually start in the legs. Late lesions may include thickening of the skin and subcutaneous tissues, visceral fibrosis, and finally severe symptoms like limb contracture, cachexia, and death (8, 9). However, the detailed mechanisms remain largely unknown. The main purpose of the current study was to explore whether high 603 This article is freely accessible online.