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 ۲۴ mature male rats were divided into ۴ groups (۶ rats in each group): Group I (control) received a normal saline solution for ۱۸ days during the study. On the ۱۵th day of the study, group II (MTX-treated) rats got a single intraperitoneal (IP) injection of MTX (۴۰ mg/kg). They were left untreated for three days. Group III was the protective group (FA+MTX). The rats were given FA (۶۰ mg/kg/d, orally) for ۱۴ days before receiving a single IP injection of MTX (۴۰ mg/kg) on day ۱۵. Group IV was the therapeutic group (MTX+FA). After three days of MTX administration (days ۱۵, ۱۶, and ۱۷), they received FA (۶۰ mg/kg/day, orally).Results: FA significantly attenuated MTX-induced biochemical and histological anomalies, as demonstrated by decreased levels of IL-۱β and caspase ۳, elevated levels of IL-۱۰, 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-۱β and caspase ۳, along with decreased levels of IL-۱۰, thereby impairing tissue architecture. FA, given either prophylactically or therapeutically, significantly reduced inflammation and apoptosis.

کلیدواژه ها:

Apoptosis ، Ferulic acid (FA) ، inflammation ، Methotrexate (MTX) ، Submandibular gland