Effects of empagliflozin on a model of chronic depression and brain Toll-like receptors gene expression in male rats

Background: Empagliflozin is an antidiabetic medication having anti-inflammatory and antioxidant properties. Objectives: To develop a chronic unpredictable stress (CUS) model in male rats, evaluate empagliflozin’s antidepressant effects, and describe the link between stress, an antioxidant enzyme, and Toll-like receptor (TLR)-4 gene expression in male rats. Materials and Methods: In this experiment, 50 rats were divided into five groups: G1–G5. The forced swimming test (FST) was used to examine the antidepressant effects of fluoxetine and empagliflozin, and real-time polymerase chain reaction was used to measure TLR-4 gene expression. FST was performed on each rat on days 0, 10, and 25. CUS was performed on each rat for 24 days. Results: By the end of day 10, all animals subjected to the CUS program had a substantial (P < 0.05) increase in immobility duration compared with day 0. The immobility duration in the CUS group was statistically significantly greater than the baseline. Stressed rats demonstrated a statistically significant reduction in immobility duration compared with CUS group G2. In comparison to the CUS group, fluoxetine significantly reduced immobility duration (P < 0.05). In terms of gene expression, the mean of fold changes in TLR-4 mRNA level in group 2 was considerably greater than in group 1. When compared with group 2, the means of the fold changes in TLR-4 mRNA level were considerably lower in groups 3, 4, and 5. Conclusions: Empagliflozin has antidepressant-like effects and can counteract the impact of stress-induced TLR-4 overexpression in the hippocampus and elevate the activity of antioxidant enzymes in the brains of depressed rats.