University of Tehran Iranian Journal of Veterinary Medicine 2251-8894 20 2 2026 03 01 Ferulic Acid and Submandibular Salivary Gland in Rats Exposed to Methotrexate 329 338 106024 10.32598/ijvm.20.2.1005829 EN Maha Talal Fattah Department of Dental Basic Sciences, College of Dentistry, University of Mosul, Mosul, Iraq. Rana Khairi Attarbashee Department of Dental Basic Sciences, College of Dentistry, University of Mosul, Mosul, Iraq. 0000-0003-2608-4903 Faehaa Azher Al-Mashhadane Department of Dental Basic Sciences, College of Dentistry, University of Mosul, Mosul, Iraq. Journal Article 2025 06 12 <strong>Background</strong>: Widely used in chemotherapy, methotrexate (MTX) is known to induce oxidative stress and cell death in non-target organs, such as salivary glands. <br /><strong>Objectives</strong>: This study investigates the preventive and therapeutic effects of ferulic acid (FA), a naturally occurring antioxidant and anti-inflammatory compound, on the histological and biochemical alterations induced by MTX in the submandibular salivary glands of rats. <br /><strong>Methods</strong>: A total of 24 mature male rats were divided into 4 groups (6 rats in each group): Group I (control) received a normal saline solution for 18 days during the study. On the 15th day of the study, group II (MTX-treated) rats got a single intraperitoneal (IP) injection of MTX (40 mg/kg). They were left untreated for three days. Group III was the protective group (FA+MTX). The rats were given FA (60 mg/kg/d, orally) for 14 days before receiving a single IP injection of MTX (40 mg/kg) on day 15. Group IV was the therapeutic group (MTX+FA). After three days of MTX administration (days 15, 16, and 17), they received FA (60 mg/kg/day, orally).<br /><strong>Results</strong>: FA significantly attenuated MTX-induced biochemical and histological anomalies, as demonstrated by decreased levels of IL-1β and caspase 3, elevated levels of IL-10, and attenuated degenerative alterations in the granular convoluted tubule, mucous acini, and striate duct.<br /><strong>Conclusion</strong>: The study revealed that MTX induces inflammation and cellular death in the submandibular salivary glands of rats, as evidenced by increased levels of IL-1β and caspase 3, along with decreased levels of IL-10, thereby impairing tissue architecture. FA, given either prophylactically or therapeutically, significantly reduced inflammation and apoptosis.  https://ijvm.ut.ac.ir/article_106024_9a5ca6dfeb49223b938732b1dd8cc07a.pdf