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Neuropeptide W Attenuates Oxidative Multi-Organ Injury in Rats Induced with Intra-Abdominal Sepsis

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Abstract—

Sepsis leads to systemic hypotension, disturbed perfusion, inflammation, and tissue toxicity in vital organs. Neuropeptide W (NPW) has modulatory effects in the control of blood pressure and inflammatory processes, implicating a potential beneficial effect against sepsis-induced oxidative damage. Under anesthesia, male Sprague Dawley rats underwent cecal ligation and puncture. Immediately after surgery, either saline or TNF-alpha inhibitor (etanercept; 1 mg/kg) antibiotic (ceftriaxon; 10 mg/kg) combination or NPW (0.1, 1, or 3 μg/kg) was given subcutaneously, and injections were repeated on the 12th and 24th h. The sham-operated control group was treated with saline at the same time points. All rats were euthanized on the 25th h of surgery. Sepsis resulted in oxidative damage of the brain, heart, lung, liver, and kidney. Elevations in blood urea nitrogen and alkaline phosphatase, showing renal and hepatic dysfunction, were not evident when septic rats were treated with NPW. NPW reduced serum levels of C-reactive protein, corticosterone, and interleukin-6, while histopathologically verified tissue damage in all the studied tissues was ameliorated. NPW treatment suppressed lipid peroxidation in the heart, lung, and brain, and the depleted antioxidant GSH levels of the brain and heart were replenished by NPW. Moreover, sepsis-related neutrophil recruitment to the liver and lung was also suppressed by NPW. Although the survival rate of the rats was not significantly prolonged by NPW, most of these improvements in systemic and local inflammatory events were comparable with those reached by the etanercept and antibiotic combination, suggesting the therapeutic impact of NPW during the acute period of sepsis.

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Availability of Data and Material

The data that support the findings of the present study are available from the corresponding author (BCY) upon request.

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Funding

The study was supported by a grant from the Marmara University Fund, Istanbul, TR (Project no. SAG-A-130319–0087).

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Authors and Affiliations

  1. Department of General Surgery, School of Medicine, Marmara Üniversitesi, Istanbul, Turkey

    Ali Emre Atici

  2. Department of Physiology, School of Medicine, Marmara University, Başıbüyük Mah. Maltepe Başıbüyük Yolu No. 9/1, 34854, Istanbul, Turkey

    Sevil Arabacı Tamer & Berrak Ç. Yeğen

  3. Department of Histology & Embryology, School of Medicine, Marmara University, Istanbul, Turkey

    Hilal Nişva Levent & Feriha Ercan

  4. Department of Medical Biology, School of Medicine, Marmara University, Istanbul, Turkey

    İrem Peker Eyüboğlu & Mustafa Akkiprik

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Contributions

All the experiments were performed at the Marmara University School of Medicine, Departments of Physiology & Histology and Medical Biology. All persons designated as authors qualify for authorship. All persons who qualify for authorship are listed. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Study conception and design of work: Ali Emre Atıcı, Sevil Arabacı Tamer, Hilal Nişva Levent, İrem Peker Eyüboğlu, Feriha Ercan, Mustafa Akkiprik, and Berrak Ç. Yeğen (all authors). Data acquisition: Ali Emre Atıcı, Sevil Arabacı Tamer, Hilal Nişva Levent, and İrem Peker Eyüboğlu. Analysis and data interpretation: all authors.

Drafting of the manuscript: all authors. Critical revision: Berrak Ç. Yeğen. Approval of the final version of the manuscript: all authors.

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Correspondence to Berrak Ç. Yeğen.

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Atici, A., Arabacı Tamer, S., Levent, H.N. et al. Neuropeptide W Attenuates Oxidative Multi-Organ Injury in Rats Induced with Intra-Abdominal Sepsis. Inflammation 45, 279–296 (2022). https://doi.org/10.1007/s10753-021-01545-5

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