A new study published in the journal Aging sheds light on a potential treatment for postmenopausal xerostomia, or dry mouth. Xerostomia is a condition commonly experienced by elderly individuals, particularly women, and its prevalence is estimated to range from 5.5%–46%. The underlying mechanism behind xerostomia after menopause is not yet fully understood.

Researchers from Pusan National University and Sungkyunkwan University School of Medicine aimed to investigate the mechanism of xerostomia and the effect of ferroptosis inhibitors deferoxamine (DFO) and ferrostatin-1 (FER) on salivary gland dysfunction in a postmenopausal animal model. In the past, it was reported that ferroptosis in the salivary gland may be linked to xerostomia after menopause, but no studies had used anti-ferroptosis drugs to investigate the mechanisms behind postmenopausal salivary gland dysfunction.

The team randomly divided 24 female Sprague-Dawley rats into four groups: a SHAM group, an OVX group, an FER group, and a DFO group. The groups were analyzed for GPX4 activity, iron accumulation, lipid peroxidation, inflammation, fibrosis, and salivary gland function.

Results of the study showed that the recovery of GPX4 activity and a decrease in iron accumulation and cytosolic MDA + HAE were observed in the DFO group. Collagen I, collagen III, TGF-β, IL-6, TNF-α, and TGF-β levels were also 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.

This study is the first to investigate the effect of ferroptosis inhibitors (DFO and FER) on the salivary glands of ovariectomized rats. Researchers concluded that DFO and FER are promising treatments for postmenopausal xerostomia. In the absence of a standard treatment for postmenopausal dry mouth, the study is expected to be helpful in understanding the mechanism of postmenopausal salivary gland dysfunction and developing a treatment for postmenopausal dry mouth.