Synergistic Effects of Metformin and Fluorouracil on Cognitive Disability via Inducing Neuroinflammation in Rat Models

Background and Objective: Fluorouracil (FU) is a potent chemotherapeutic agent commonly used in combination with other drugs to effectively combat various sorts of cancer, including breast, prostate, lung and brain cancer. The Metformin (MET) is a medication that has been found to potentially improve cognitive disability connected with diabetes and Alzheimer’s disease. This study assessed the potential preventive effects of MET on cognitive disability induced by FU. Materials and Methods: Male rats in the FU and FU+MET groups received intraperitoneal injections of FU (100 mg/kg) the control group received saline via the same route. Rats in the MET and FU+MET groups were then offered drinking water containing MET (2.5 mg/mL). The cognitive ability of rats was then evaluated in behavioral tests (Y-maze, novel object recognition, elevated plus maze), while inflammation in the hippocampus was assessed by analysis of the levels of TNF-α, IL-6 and IL-1β in enzyme-linked immunosorbent assays. Results: The findings indicated an increase in mortality and a reduction in body weight among rats treated with FU compared to the control. The FU treatment also impair memory function by decreasing the exploration of the novel arm in Y-maze and novel object in NOR tests and increasing the transfer latency in EPM. Compared with the control group, increased TNF-α, IL-6 and IL-1β levels were detected in the hippocampus of rats in the FU and FU+MET-treated groups. Conclusion: The findings indicate that FU-induced cognitive disability was caused by increased neuronal inflammation and that this effect was further enhanced by MET.