Journal of Clinical & Experimental Pharmacology

Spermidine exerts protective effects in random-pattern skin flap survival in rats

36^th World Congress on Pharmacology

July 25, 2023 | Webinar

Razieh Mohammad Jafari

Tehran University of Medical Sciences, Iran

Posters & Accepted Abstracts: J Clin Exp Pharmacol

Abstract:

Background: Distal necrosis and inflammation are two of the most common health consequences of randompattern skin flaps survival. Anti-inflammatory effects of spermidine have been identified in various studies. On the other hand, considering the involvement of the Nitric Oxide (NO) molecule in the spermidine mode of action and also its role in skin tissue function, we analyzed the possible effects of spermidine on the skin flaps survival and also, potential involvement of nitrergic pathway and inflammatory cytokine in these phenomena. Methods: In this experiment, male Wistar rats were randomized into 8 groups. 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 we executed a random-pattern skin flap paradigm. Among the mentioned different doses, 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, histopathological assessments and molecular evaluations were done. 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 (VEGF) expression was assessed by 4',6-diamidino-2-phenylindole (DAPI) staining and fluorescent microscopes. The concentrations of three polyamines, including spermidine, spermine and cadaverine, were analyzed after multiple dose administration of spermidine by HPLC. Results: Pretreatment with spermidine 5 mg/kg improved skin flaps survival considerably in microscopic skin H&E staining analysis and increased the percentage of necrotic area in macroscopic investigations in rats. Moreover, spermidine exerted promising anti-inflammatory effects via the modulation of NO and reducing inflammatory cytokines. Also, IL- 6, TNF-α, IFN-γ, was significantly decreased and nitrite levels were significantly increased compared to the control group by spermidine. Conclusions: Spermidine could improve skin flaps survival, probably through the nitrergic system as well as suppressing inflammation pathways. Therefore, in skin flap procedures, focusing on these molecular systems appears to be a reliable solution to improve tissue survival and reduce necrosis. However, in order to guarantee the secure clinical application of spermidine in this approach, more experimental and clinical studies are required.

Biography :

Razieh Mohammad Jafari has completed her Pharm-D at the age of 24 years from Tabriz University of medical sciences and now is PhD candidate from Tehran University of Medical sciences. She has published more than five papers in reputed journals and has been serving as an editorial board member of repute.