Protective effects of tumor necrosis factor alpha inhibitors on methotrexate-induced pancreatic toxicity

Methotrexate (MTX), a folate antagonist, is commonly used in the treatment of many different types of cancer and inflammatory diseases, including pancreatic cancer, although its side effects on the pancreas have not yet been researched. The mechanism of MTX-induced toxicity is not well known, and it has been reported in high-dose toxicity studies that the pancreas is sensitive to toxic effects. The aim of our study was to determine whether adalimumab (ADA) has a preventive effect on MTX-induced pancreas toxicity in rats. The rats were equally and randomly divided into 3 groups (Group 1 comprised the healthy controls, Group 2 was the MTX group, and Group 3 was the MTX + ADA group). The rats in Groups 2 and 3 received an intraperitoneal (ip.) single-dose injection of MTX (20 mg/kg). A single dose of 5 mg/kg ADA (REMICADE®) was administered ip. to Group 3. All the rats were sacrificed under anesthesia 5 days after receiving the MTX injection. Significantly higher mean edema, necrotic cell, and inflammatory scores were recorded in Groups 2 and 3 compared to those recorded in Group 1. Significantly decreased edema, number of necrotic cells, and inflammatory scores were noted in Group 3 than in Group 2. A decrease in islets of Langerhans cell insulin and somatostatin-positive interneurons was demonstrated after the administration of MTX. An increase in insulin and somatostatin-positive cells in islets of Langerhans, as well as a remodeling of the structure of the pancreas, was shown following treatment with ADA. Adalimumab was demonstrated to have a protective effect against MTX-induced pancreatic injury in this study.