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Examination of antimicrobial effect of fluoxetine in experimental sepsis model: An in vivo study
Ahsen Cakir1, Kubra Bozali2,3, Mert Celikten4,5
1Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey.
Abstract:
Since most infectious diseases can develop into sepsis, it is still a major medical problem. Some in-vivo studies showed promising properties of fluoxetine in the treatment of infections. This study aims the antimicrobial effect of fluoxetine on the inflammatory process used in the treatment of sepsis-modeled rats. Besides, to investigate the efficacy of fluoxetine on modifying the antibiotic effect of imipenem in the inflammatory response. An experimental sepsis model was divided into negative control, positive control, fluoxetine 5 mg/kg, imipenem 60 mg/kg, and combined (fluoxetine; imipenem). Procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), lactate, myeloperoxidase activity (MPO), the inflammation markers interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alfa (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) levels were measured by enzyme-linked immunosorbent assay method. Oxidative stress markers, total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), and native thiol (NT) were measured using photometric methods. Oxidative stress index (OSI) was calculated according to TAS and TOS levels. The statistical analysis was performed by Statistical Package for Social Sciences version 22.0. After treatment with fluoxetine, imipenem, and combined groups, IL-1β, IL-6, TNF-α, MPO activity, MCP-1, hs-CRP, PCT, lactate, and the oxidative stress markers OSI, and disulfide levels were decreased (p < 0.05). The TT, NT, and TAS levels significantly statistically increased (p < 0.05). This research demonstrates that fluoxetine has effects as anti-inflammatory and antioxidant, and the combined treatment with antibioticum imipenem indicates positive synergistic effects in the experimental sepsis model.
Insights
Fluoxetine exhibits anti-inflammatory and antioxidant effects, reducing sepsis markers in rats. Combined with imipenem, it shows synergistic benefits in treating experimental sepsis.
Area of Science:
- Pharmacology
- Immunology
- Biochemistry
Background:
- Sepsis, a life-threatening condition, arises from infections and presents a major medical challenge.
- In-vivo studies suggest fluoxetine possesses properties beneficial for treating infections.
- Investigating fluoxetine's role in sepsis management, particularly its anti-inflammatory and antioxidant potential, is crucial.
Purpose of the Study:
- To evaluate the antimicrobial and anti-inflammatory effects of fluoxetine in a rat model of sepsis.
- To assess fluoxetine's impact on key inflammatory and oxidative stress markers in sepsis.
- To determine if fluoxetine enhances the efficacy of imipenem in treating sepsis-induced inflammation.
Main Methods:
- An experimental sepsis model was established in rats, divided into control and treatment groups (fluoxetine, imipenem, combined).
- Levels of inflammatory markers (PCT, hs-CRP, IL-1β, IL-6, TNF-α, MCP-1), lactate, and MPO activity were measured.
- Oxidative stress markers (TOS, TAS, TT, NT, OSI) were quantified using photometric and ELISA methods.
Main Results:
- Fluoxetine, imipenem, and their combination significantly reduced inflammatory markers (IL-1β, IL-6, TNF-α, MCP-1, hs-CRP, PCT, lactate, MPO activity).
- Oxidative stress markers, including OSI and disulfide levels, were decreased in the treatment groups.
- Total thiol (TT), native thiol (NT), and total antioxidant status (TAS) levels were significantly increased, indicating improved antioxidant capacity.
Conclusions:
- Fluoxetine demonstrates significant anti-inflammatory and antioxidant properties in an experimental sepsis model.
- Combined treatment with fluoxetine and imipenem exhibited synergistic effects, improving outcomes in sepsis.
- These findings suggest fluoxetine as a potential adjunctive therapy for sepsis management.
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