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

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  • Basic Science/Experimental
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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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Data availability

Data will be shared by request.

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Acknowledgements

This work was supported by a grant from Experimental Medicine Research Center, Tehran University of Medical Sciences (Grant No. 1400-2-209-54847) and Iran National Science Foundation. Special thanks to Iran National Science Foundation (INSF) for their support.

Author information

Authors and Affiliations

  1. Student Research Committee, Tehran University of Medical Sciences, Tehran, Iran

    Kimiya Jouyban

  2. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, 131145-784, Iran

    Kimiya Jouyban, Razieh Mohammad Jafari, Mohammad Amin Manavi & Ahmad Reza Dehpour

  3. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Razieh Mohammad Jafari & Ahmad Reza Dehpour

  4. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Amin Manavi

  5. Drug Applied Research Center, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

    Mohammad Charkhpour

  6. Pharmaceutical Analysis Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Hadis Rezaei & Behrouz Seyfinejad

  7. Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Seyed Mohammad Tavangar

  8. Department of Intensive Care, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran

    Seyed Mohammad Tavangar

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Contributions

AD and RMJ contributed to study conception and design. KJ, RMJ, BS, MC, ST, and HR contributed to acquisition of data. KJ, HR, MM, ST, and RMJ contributed to analysis and interpretation of data. KJ, MM, RMJ, MC, MB, and HR contributed to drafting of manuscript. RMJ, MM, MC, BS, AD, and ST contributed to critical revision, and RMJ obtained funding.

Corresponding authors

Correspondence to Razieh Mohammad Jafari or Ahmad Reza Dehpour.

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This study was approved by the Ethics in Medical Research Committee of Tehran University of Medical Sciences (IR.TUMS.VCR.REC.1400-821).

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Jouyban, K., Mohammad Jafari, R., Charkhpour, M. et al. Spermidine Exerts Protective Effects in Random-Pattern Skin Flap Survival in Rats: Possible Involvement of Inflammatory Cytokines, Nitric Oxide, and VEGF. Aesth Plast Surg (2024). https://doi.org/10.1007/s00266-024-04119-6

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