Investigating the Effect of Sertraline on Pancreatic Injury in Male Rats

Introduction: SSRIs, including sertraline, are primarily used for treating depres-sion and are also prescribed for conditions such as obsessive-compulsive disorder (OCD). While effective, its potential to induce pancreatic injury, as suggested by case reports, requires further investigation. Therefore, the present study investigates the effect of different thera-peutic concentrations of sertraline on pancreatic injury in rats to remove all confounding fac-tors and perform future therapeutic intervention studies if necessary. Methods: Forty male Wistar rats (8 weeks old, 250-280 g) were randomly divided into five groups (n=8): a control group and four groups receiving daily oral sertraline at doses of 20, 50, 100, or 200 mg/kg for two months. Blood samples were analyzed for glucose, insulin, amylase, lipase, malondialdehyde (MDA), and superoxide dismutase (SOD) levels. Results: Administration of sertraline resulted in a significant, dose-dependent increase in blood glucose, insulin, lipase, and MDA levels. A dose-dependent decrease in SOD activity was also observed. While amylase levels increased, the change was not statistically significant across all groups. The most pronounced effects were seen at the highest dose (200 mg/kg). Discussion: The results demonstrate that sertraline disrupts both endocrine (hyperglycemia, hyperinsulinemia) and exocrine (elevated lipase) pancreatic function, and induces systemic oxidative stress. This provides mechanistic evidence supporting clinical case reports of ser-traline-associated pancreatitis. The findings suggest that oxidative stress is a key pathway in sertraline-induced pancreatic injury. Conclusion: The findings indicate that sertraline induces pancreatic injury and oxidative stress in rats in a dose-dependent manner, supporting clinical observations of its potential pancreatotoxic effects.