Research Paper|Volume 15, Issue 7|pp 2418—2432

Effect of deferoxamine and ferrostatin-1 on salivary gland dysfunction in ovariectomized rats

Yong-Il Cheon¹, Ji Min Kim², Sung-Chan Shin¹, Hyung-Sik Kim⁴, Jin-Choon Lee³, Gi Cheol Park⁵, Eui-Suk Sung³, Minhyung Lee³, Byung-Joo Lee¹

¹Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Pusan National University and Medical Research Institute, Pusan National University Hospital, Busan, Korea
²Pusan National University Medical Research Institute, Pusan National University School of Medicine, Busan, Korea
³Department of Otorhinolaryngology-Head and Neck Surgery, College of Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
⁴Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, Korea
⁵Department of Otolaryngology-Head and Neck Surgery, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea

* Equal contribution

Received: September 30, 2022Accepted: March 28, 2023Published: April 6, 2023

https://doi.org/10.18632/aging.204641

Copyright: © 2023 Cheon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The mechanism underlying xerostomia after menopause has not yet been fully elucidated. This study aimed to investigate the mechanism of xerostomia and the effect of the ferroptosis inhibitors deferoxamine (DFO) and ferrostatin-1 (FER) on salivary gland dysfunction in a postmenopausal animal model. Twenty-four female Sprague–Dawley rats were randomly divided into four groups: a SHAM group (n = 6, sham-operated rats), an OVX group (n = 6, ovariectomized rats), an FER group (n = 6, ovariectomized rats injected intraperitoneally with FER), and a DFO group (n = 6, ovariectomized rats injected intraperitoneally with DFO). GPX4 activity, iron accumulation, lipid peroxidation, inflammation, fibrosis, and salivary gland function were analyzed. Recovery of GPX4 activity and a decrease in iron accumulation and cytosolic MDA + HAE were observed in the DFO group. In addition, collagen I, collagen III, TGF-β, IL-6, TNF-α, and TGF-β levels were decreased in the DFO group compared to the OVX group. Recovery of GPX4 activity and the morphology of mitochondria, and reduction of cytosolic MDA + HAE were also observed in the FER group. In addition, decreased expression of inflammatory cytokines and fibrosis markers and increased expression of AQP5 were observed in both the DFO and FER groups. Postmenopausal salivary gland dysfunction is associated with ferroptosis, and DFO and FER may reverse the postmenopausal salivary gland dysfunction after menopause. DFO and FER are hence considered promising treatments for postmenopausal xerostomia.