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Aesthetic Plastic Surgery

16-05-2024 | Cytokines | Original Articles

Spermidine Exerts Protective Effects in Random-Pattern Skin Flap Survival in Rats: Possible Involvement of Inflammatory Cytokines, Nitric Oxide, and VEGF

Authors: Kimiya Jouyban, Razieh Mohammad Jafari, Mohammad Charkhpour, Hadis Rezaei, Behrouz Seyfinejad, Mohammad Amin Manavi, Seyed Mohammad Tavangar, Ahmad Reza Dehpour

Published in: Aesthetic Plastic Surgery

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Abstract

Background

Distal necrosis and inflammation are two of the most common health consequences of random-pattern skin flaps survival (SFS). Anti-inflammatory effects of spermidine have been identified in various studies. On the other hand, considering the involvement of the nitric oxide molecule in the spermidine mode of action and also its role in skin tissue function, we analyzed the possible effects of spermidine on the SFS and also, potential involvement of nitrergic pathway and inflammatory cytokine in these phenomena.

Methods

Each rat was pretreated with either a vehicle (control) or various doses of spermidine (0.5, 1, 3, 5, 10 and 30 mg/kg) and then was executed a random-pattern skin flap paradigm. Also, spermidine at the dose of 5 mg/kg was selected and one group rats received spermidine 20 min prior to surgery and one additional dose 1 day after operation. Then, 7 days after operations, interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon-gamma (IFN-γ), and nitrite levels were inquired in the tissue samples by ELIZA kit. Vascular endothelial growth factor expression was assessed by DAPI staining and fluorescent microscopes. The concentrations of three polyamines, including spermidine, spermine, and cadaverine, were analyzed using HPLC.

Results

Pretreatment with spermidine 5 mg/kg improved SFS considerably in microscopic skin H&E staining analysis and decreased the percentage of necrotic area. Moreover, spermidine exerted promising anti-inflammatory effects via the modulation of nitric oxide and reducing inflammatory cytokines.

Conclusions

Spermidine could improve skin flaps survival, probably through the nitrergic system and inflammation pathways. This preclinical study provides level III evidence for the potential therapeutic effects of spermidine on SFS in rats, based on the analysis of animal models. Further studies are needed to confirm these findings in clinical settings.

Level of Evidence III

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.​springer.​com/​00266.
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Metadata
Title
Spermidine Exerts Protective Effects in Random-Pattern Skin Flap Survival in Rats: Possible Involvement of Inflammatory Cytokines, Nitric Oxide, and VEGF
Authors
Kimiya Jouyban
Razieh Mohammad Jafari
Mohammad Charkhpour
Hadis Rezaei
Behrouz Seyfinejad
Mohammad Amin Manavi
Seyed Mohammad Tavangar
Ahmad Reza Dehpour
Publication date
16-05-2024
Publisher
Springer US
Keyword
Cytokines
Published in
Aesthetic Plastic Surgery
Print ISSN: 0364-216X
Electronic ISSN: 1432-5241
DOI
https://doi.org/10.1007/s00266-024-04119-6