Spermidine Protects against Oxidative Stress in Inflammation Models Using Macrophages and Zebrafish

• Published in: Biomolecules & therapeutics Vol. 26; no. 2; pp. 146 - 156
• Main Authors: Jeong, Jin-Woo, Cha, Hee-Jae, Han, Min Ho, Hwang, Su Jung, Lee, Dae-Sung, Yoo, Jong Su, Choi, Il-Whan, Kim, Suhkmann, Kim, Heui-Soo, Kim, Gi-Young, Hong, Su Hyun, Park, Cheol, Lee, Hyo-Jong, Choi, Yung Hyun
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Society of Applied Pharmacology 01.03.2018; 한국응용약물학회
• Subjects: Original; 약학; Zebrafish; Anti-Inflammation; Macrophages; Anti-Oxidant; Spermidine
• ISSN: 2005-4483; 1976-9148; 1976-9148; 2005-4483
• DOI: 10.4062/biomolther.2016.272

Spermidine is a naturally occurring polyamine compound that has recently emerged with anti-aging properties and suppresses inflammation and oxidation. However, its mechanisms of action on anti-inflammatory and antioxidant effects have not been fully elucidated. In this study, the potential of spermidine for reducing pro-inflammatory and oxidative effects in lipopolysaccharide (LPS)-stimulated macrophages and zebrafish was explored. Our data indicate that spermidine significantly inhibited the production of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin E (PGE ), and cytokines including tumor necrosis factor-α and interleukin-1β in RAW 264.7 macrophages without any significant cytotoxicity. The protective effects of spermidine accompanied by a marked suppression in their regulatory gene expression at the transcription levels. Spermidine also attenuated the nuclear translocation of NF-κB p65 subunit and reduced LPS-induced intracellular accumulation of reactive oxygen species (ROS) in RAW 264.7 macrophages. Moreover, spermidine prevented the LPS-induced NO production and ROS accumulation in zebrafish larvae and was found to be associated with a diminished recruitment of neutrophils and macrophages. Although more work is needed to fully understand the critical role of spermidine on the inhibition of inflammation-associated migration of immune cells, our findings clearly demonstrate that spermidine may be a potential therapeutic intervention for the treatment of inflammatory and oxidative disorders.