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Publications

Journal Article Ahead of print

PubMed: 41022339 DOI: 10.1016/j.toxlet.2025.111733

Pre-clinical safety assessments of gadobutrol in diabetes-induced neuropathy: In vivo, in vitro and in silico studies.

Toxicol Lett 413:111733

Authors: Batuhan Bilgin, Munevver Gizem Hekim, Muhammed Adam, Ferah Bulut, Seval Ulku Orhan, Suat Tekin, Mehmet Tahir Husunet, Mete Ozcan

Affiliations

  • Gaziantep Islam Science and Technology University Faculty of Medicine, Department of Biophysics, Gaziantep, Turkey.
  • Firat University Faculty of Medicine, Department of Physiology, Elazig, Turkey.
  • Firat University Faculty of Medicine, Department of Biophysics, Elazig, Turkey.
  • Firat University Faculty of Medicine, Department of Biophysics, Elazig, Turkey.
  • Firat University Faculty of Medicine, Department of Biophysics, Elazig, Turkey.
  • Inonu University Faculty of Medicine, Department of Physiology, Malatya, Turkey.
  • Gaziantep Islam Science and Technology University Faculty of Medicine, Department of Medical Genetics, Gaziantep, Turkey.
  • Firat University Faculty of Medicine, Department of Biophysics, Elazig, Turkey.

Abstract

Due to its vascular complications, patients with diabetes mellitus (DM) are exposed to gadobutrol in imaging. However, the safety concerns of gadobutrol to diabetes-induced neuropathy, a common complication of DM, remain unclear as a scientific gap. This study aimed to investigate the effects of gadobutrol on hypersensitivity in a streptozotocin (STZ)-induced diabetic neuropathy model in mice and its effects on cytotoxicity and genotoxicity in high glucose (HG)-induced neuropathy in dorsal root ganglion (DRG) neurons. Adult (6-8 weeks old) BALB/c male mice were intraperitoneally administered STZ (150 mg/kg) and hot plate, cold plate, von Frey, and rota rod tests were performed 21 days after blood glucose levels rose above 250 mg/dL (N = 40). Gadobutrol was administered intravenously. DRG neurons were isolated from neonatal Sprague-Dawley rats and HG (45 mmol/L) was administered. Subsequently, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and comet assay were performed on gadobutrol-treated and HG-exposed DRG neurons. Furthermore, molecular docking analysis was performed between gadobutrol and catalase (CAT). STZ + gadobutrol showed a statistically significant increase in sensitivity in hot plate, cold plate and von Frey assays compared to STZ (p = 0.0013, p = 0.0019 and p = 0.0189, respectively). HG + gadobutrol showed statistically significant increases in cytotoxicity and genotoxicity compared to HG. The binding affinity of gadobutrol to CAT was determined as - 8.59 kcal/mol. The results of this study suggest for the first time that gadobutrol can exacerbate diabetes-induced neuropathy. Further clinical studies are needed to elucidate these results, which may pose a new safety concern for patients with diabetic neuropathy.

MeSH

Diabetes Mellitus, Safety, Neurons, Cold Temperature, Diabetic Neuropathies, Toxicology