Ameliorative Effect of Ezetimibe on Inflammatory and Apoptotic Biomarkers in Methotrexate-Induced Salivary Gland Injury

Background: Methotrexate (MTX) is a chemotherapeutic agent used to treat various malignancies and autoinflammatory conditions. MTX have an adverse effect on oral tissues, particularly by compromising salivary gland (SG) function. Ezetimibe is a lipid-lowering medication that has more potent anti-inflammatory, and anti-apoptotic effects. Aims: This research aimed to assess the protective effects of ezetimibe on SG in rats subjected to MTX -induced alterations. Methods: A total of 18 male albino rats were haphazardly assigned into 3 groups. Group I (vehicle control) received normal saline solution for 10 days, while the group II was induced by MTX injection (20 mg/kg, single intraperitoneal, i.p.) on the sixth day of the experiment. Group III (Ezetimibe+ MTX) received oral Ezetimibe 10 mg/kg once daily for 10 days. SG tissues from rats were collected on day 11 and euthanized for biochemical and immunohistochemical (IHC) testing. Results: Ezetimibe significantly ameliorated the biochemical and IHC dysregulation caused by MTX, as evidenced by reduced levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and an elevation in B-cell lymphoma 2 (Bcl-2) level. Conclusions: Ezetimibe is an anti-inflammatory and antiapoptotic agent that may be a promising approach to reducing MTX toxicity in submandibular glandular tissue.