Induction of oxidative stress and functional impairment by Doxorubicin in rat salivary glands

Abstract

This study investigated the impact of doxorubicin (Dox) on the functional, biochemical, and redox parameters of salivary glands in rats. Male Wistar rats (six weeks old and approximately 240 g) were randomly allocated into three groups (n = 12/group): Control (saline solution), Dox2.5 (2.5 mg/kg), and Dox5.0 (5.0 mg/kg, equivalent to the human therapeutic dose of 20 mg/m2). Treatments were administered weekly via intraperitoneal injection for three consecutive weeks. One week after the final administration, pilocarpine-stimulated saliva was collected, and the parotid and submandibular glands were harvested for analysis. Both Dox-treated groups showed decreases in body weight and salivary gland weight; however, only Dox5.0 reduced feed intake, decreased the parotid acinar area, and increased connective tissue septa. Saliva assessment demonstrated that Dox5.0 decreased flow rate, total protein, amylase, calcium, phosphate, and chloride, while Dox2.5 reduced total protein and amylase; sodium and potassium levels, pH, and buffering capacity remained unchanged. Dox5.0 increased total oxidant status and lipid and protein oxidative damage in parotid glands, as well as uric acid, reduced glutathione, superoxide dismutase, catalase, and glutathione peroxidase. Analysis of submandibular glands showed that Dox5.0 elevated total oxidant status, uric acid, and catalase, while Dox2.5 increased uric acid and catalase in the parotid gland. These findings indicate that Dox impairs both the quantity and quality of saliva, promoting oxidative stress and structural alterations, particularly in the parotid glands, with more pronounced effects at the 5.0 mg/kg dose.