The Role of Endoplasmic Reticulum Stress in Cell Injury Induced by Methimazole on Pancreatic Cells

Yazıcı Ö., Kara M., Boran T., Özhan G.

ADVANCED PHARMACEUTICAL BULLETIN, cilt.13, sa.1, ss.196-201, 2023 (ESCI)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 13 Sayı: 1
  • Basım Tarihi: 2023
  • Doi Numarası: 10.34172/apb.2023.042
  • Dergi Adı: ADVANCED PHARMACEUTICAL BULLETIN
  • Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), Scopus, Academic Search Premier, CAB Abstracts, EMBASE, Veterinary Science Database, Directory of Open Access Journals
  • Sayfa Sayıları: ss.196-201
  • İstanbul Üniversitesi Adresli: Evet

Özet

Purpose: Methimazole is an anti-thyroid agent, especially as main therapy option for Graves’disease in children and adults. Drug induced pancreatitis is one of the known adverse effect of methimazole mentioned in case reports. However, the detailed molecular mechanisms of methimazole-induced pancreatitis are still unclear. In this study, the aim is to investigate the adverse effect of methimazole on pancreas cell stress mechanism and apoptosis.

Methods: Cytotoxicity was evaluated in human pancreas/duct (PANC-1) cell line. Total oxidant (TOS) and antioxidant status (TAS) for oxidative stress index, glutathione (GSH) level and endoplasmic reticulum (ER) stress biomarkers were evaluated by ELISA. Reactive oxygen species (ROS) levels and apoptosis were evaluated by flow-cytometer.

Results: The 30% inhibition rate concentration (IC30) value was determined as 53 mM in PANC-1 cells. The exposure concentrations were in the range of 0-40 mM for 48 hours. Methimazolemight induce cellular stress conditions. ROS production increases depending on concentration, and this increase shows parallelism with the increase in ER stress biomarkers such as TOS, ERN1 and CASPASE12. Conversely, there was no significant difference between control and exposure groups in terms of apoptosis.

Conclusion: In conclusion, methimazole might have triggered the mechanisms of inflammation or autophagy in the pancreatic cells. However, there is still a need for in vitro and in vivo studies including other cellular parameters related to apoptosis.