European Archives of Oto-Rhino-Laryngology

, Volume 275, Issue 6, pp 1641–1647 | Cite as

Effects of gadolinium-based contrast agents on submandibular gland tissue in rats

  • Fatma Beyazal Celiker
  • Levent Tumkaya
  • Adnan Yilmaz
  • Zerrin Ozergin Coskun
  • Metin Celiker
  • Fatih Oghan
  • Tolga Mercantepe
  • Suat Terzi
  • Engin Dursun



The aim of this prospective animal study is to investigate the influence of multiple administrations of macrocyclic ionic (gadoteric acid) and linear nonionic (gadodiamide) gadolinium-based contrast agents (GBCA) on submandibular gland tissue (SGT) of the rats.

Material and method

Twenty-four Sprague Dawley female rats were included the study. Group 1 was determined as a control group (n = 6). Group 2 was determined as saline group (n = 6). Group 3 was determined as Omniscan group (n = 6) and received only intraperitoneal (IP) 0.1 mmol (0.2 mL/kg)/kg gadodiamide for 8 days. Group 4 was determined as Dotarem group (n = 6) and received only IP 0.1 mmol (0.2 mL/kg)/mg/kg gadoteric acid daily for 8 days. On the 9th day of the administration, the rats were sedated with ketamine and xylazine through IP injection. The right SGT was removed after sedation. Histopathological and immunohistochemical changes in SGT were evaluated.


The SGT of the Omniscan and Dotarem groups decreased SGT acini surface area, and serous acinar cells number were observed. On the other hand, no pathology was observed. Mucous acinar cells’ caspase-3 positivity for the same markers in Omniscan and Dotarem sections was similar to the control group. However, Omniscan and Dotarem groups serous acinar cells were caspase-3 (+) staining. The intensity of serous acinar cells’ caspase-3 (+) for the same markers in Dotarem sections was similar to the Omniscan group. The results also revealed in the analysis of the mean area of the acinus area of the SGT; there were significantly decreased Dotarem group rats when compared to control rats (p < 0.05).


We consider that numerical increased apoptosis results arise from repeated doses of GBCAs. Being aware of this effect of the contrast agent may have significance for the chronic sialo-adenitis patients group when used for recurrent contrasted MRI for diagnosis of diseases like MS which requires in follow-up. We should be aware about the frequently contrasted MRI in routine investigations.


Gadolinium Submandibular gland Contrast Rat 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

This research involving animals was approved by Animal Ethical Committee with the number of 2016/7. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

Informed consent

Animal welfares were obtained.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Fatma Beyazal Celiker
    • 1
  • Levent Tumkaya
    • 2
  • Adnan Yilmaz
    • 3
  • Zerrin Ozergin Coskun
    • 4
  • Metin Celiker
    • 4
  • Fatih Oghan
    • 5
  • Tolga Mercantepe
    • 2
  • Suat Terzi
    • 4
  • Engin Dursun
    • 4
  1. 1.Department of Radiology, Faculty of MedicineRecep Tayyip Erdogan UniversityRizeTurkey
  2. 2.Department of Histology-Embriology, Faculty of MedicineRecep Tayyip Erdogan UniversityRizeTurkey
  3. 3.Department of Biochemistry, Faculty of MedicineRecep Tayyip Erdogan UniversityRizeTurkey
  4. 4.Department of Otorhinolaryngology, Faculty of MedicineRecep Tayyip Erdogan UniversityRizeTurkey
  5. 5.Department of ORL & HNS, Faculty of MedicineDumlupinar UniversityKutahyaTurkey

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