ferulic acid and submandibular salivary gland in rats exposed to methotrexate

Background: widely used in chemotherapy, methotrexate (mtx) is known to induce oxidative stress and cell death in non-target organs, such as salivary glands. objectives: 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. methods: 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).results: 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.conclusion: 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.