The Possible effect of Bosentan on the methotrexate-induced salivary gland changes in male rats: histological and Immunohistochemical study

Abstract Methotrexate (MTX) is an antimetabolite drug utilized for managing a variety of cancers and autoinflammatory conditions. MTX may trigger detrimental effects in mout, h tissues, including salivary gland impairment. Bosentan (BOS), a drug that blocks endothelin receptors, has strengthened antioxidant, anti-inflammatory, and anti-apoptotic properties. The study aimed to estimate the protective effect of BOS on MTX-exacerbated salivary changes in Wistar Albino rats. Thirty male rats were arbitrarily sorted into three groups of ten animals each. The control group received a normal saline for 18 days. The MTX (induction) group received MTX (25 mg/kg) intraperitoneally on the 7th day of the experiment once daily for 6 consecutive days. The MTX + BOS group received BOS (50 mg/kg) orally once a day for 18 days: 6 days before induction, 6 days 2-h after induction, and 6 days post-induction. Animals were euthanized on day 19, and salivary gland tissues were dissected for biochemical, histopathological, and immunohistochemical analyses. BOS dramatically improved MTX-aggravated biochemical and histopathological abnormalities, as evidenced by diminished Bax, caspase 3, TNF-α, IL-1β, MDA, and MPO levels, increased SOD, GSH, and GPX levels, and reduced degenerative changes in the granular convolute tubule, mucous acini, and striate duct. BOS further substantially upregulated MTX-induced decline of the Ki-67 and Bcl-2, as indicated by immunohistochemistry scoring methods. The anti-oxidative, ant-inflammatory, and antiapoptotic properties of BOS are a promising strategy for ameliorating the toxic effect of MTX on submandibular glandular tissues.