Background and Purpose: Some studies showed that fluoxetine has some
promising properties in the treatment of specific infections; however,
its effects have not been studied in the sepsis model. This research
aims to investigate the effect of fluoxetine on the inflammatory process
in a sepsis model in rats and to investigate its efficacy in modifying
the antibiotic effect of imipenem. Experimental Approach: 40 rats were
equally divided into five groups. The first group is as a negative
control, group 2 is a positive control, group 3 treated with fluoxetine
5mg/kg, group 4 treated with Imipenem antibiotic 60mg/kg, and group 5
treated with fluoxetine combined with imipenem for 72 hours. The
expression level of serum and tissue HsCRP, pro-calcitonin (PCT),
lactate, myeloperoxidase activity (MPO), interleukin-1β (IL-1β),
interleukin-6 (IL-6), tumor necrosis factor (TNFα), and monocyte
chemoattractant protein-1 (MCP-1) was measured using ELISA. Oxidative
stress markers were measured using photometric methods, total thiol
(TT), native thiol (NT), total oxidant status (TOS), and total
antioxidant status (TAS). Total tissue protein concentrations were
measured by the Bradford method. Key Results: In fluoxetine, imipenem,
and combined (fluoxetine + imipenem) groups, the IL-1β, IL-6, TNF-α,
MPO, MCP-1, HsCRP, PCT, lactate, TOS, OSI, and disulfide levels were
reduced (p<0.05). The antioxidant indicator (TT, NT, and TAS)
levels significantly increased (p<0.05). Fluoxetine and
imipenem combined therapy showed positive synergistic effects.
Conclusion and Implications: This research shows that fluoxetine has an
anti-inflammatory and antioxidant effect and its combined therapy with
imipenem shows positive synergistic effects in the experimental sepsis
model.