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ORAL SPERMINE ADMINISTRATION INHIBITS NITRIC OXIDE-MEDIATED INTESTINAL DAMAGE AND LEVELS OF SYSTEMIC INFLAMMATORY MEDIATORS IN A MOUSE ENDOTOXIN MODEL
Abstract
Enhanced intestinal nitric oxide production observed during sepsis is thought to play a central role in lipopolysaccharide-induced intestinal damage. In contrast intestinal polyamines, both from endogenous and exogenous origin, are essential for the maintenance of mucosal integrity. Polyamines have been shown to inhibit lipopolysaccharide-induced nitric oxide release in vitro and have been claimed to exert additional antiinflammatory actions. In this study, the effect of the polyamine spermine on the release of the proinflammatory mediators nitric oxide and tumor necrosis factor-alpha by a murine macrophage cell line was investigated. Furthermore, we investigated whether oral spermine administration inhibits lipopolysaccharide-induced intestinal inducible nitric oxide synthase and nitrotyrosine expression and modulates the release of inflammatory mediators. Our results show that although spermine inhibited lipopolysaccharide-induced nitric oxide release in a murine macrophage cell line, no effect on tumor necrosis factor-alpha release was observed. In addition, oral spermine administration inhibited intestinal inducible nitric oxide synthase and nitrotyrosine expression suggesting a protective effect of spermine on lipopolysaccharide-induced intestinal damage. In parallel a decrease in serum levels of the proinflammatory mediators nitrate, nitrite, and interferon-gamma and an increase in the antiinflammatory cytokine interleukin-10 was observed, although tumor necrosis factor-alpha levels were unaffected. These results indicate that spermine inhibits lipopolysaccharide-induced nitric oxide release in vitro as well as in vivo. Further, intraluminally derived polyamines modulate the systemic immune response. It is concluded that oral spermine administration might have therapeutic perspectives for several disorders characterized by systemic inflammation and intestinal damage.
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“spermine administration exhibits protective anti-inflammatory effects in mouse models of both localized and systemic inflammation (Steege et al., 1999; M. Zhang et al., 1997; S. Zhu et al., 2009).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Steege et al., 1999
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Spermidine in health and disease
Madeo, F., Eisenberg, T., Pietrocola, F., & Kroemer, G. (2018) · Science · doi:10.1126/science.aan2788 · Cited by 1,154
Postler, T. S., & Ghosh, S. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.05.008 · Cited by 876
“Indeed, spermine administration exhibits protective anti-inflammatory effects in mouse models of both localized and systemic inflammation (ter Steege et al., 1999; Zhang et al., 1997; Zhu et al., 2009).”
BackgroundGreenacre, S., & Ischiropoulos, H. (2001) · Free Radical Research · doi:10.1080/10715760100300471 · Cited by 500
Toxicity of Polyamines and Their Metabolic Products
Pegg, A. E. (2013) · Chemical Research in Toxicology · doi:10.1021/tx400316s · Cited by 306
Emerging avenues linking inflammation and cancer
Kundu, J. K., & Surh, Y. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.02.035 · Cited by 272
Metadata
- Authors
- ter Steege, J. C. A., Forget, P. P., & Buurman, W. A.
- Affiliations
- Maastricht University Medical Centre (NL)
- Maastricht University (NL)
- Corresponding author
- Forget, P. Ph.
- ORCID
- Buurman, W. A.
- Venue
- Shock
- Published
- 1999-02
- Volume
- 11
- Issue
- 2
- Pages
- 115-119
- ISSN
- 1073-2322 (ISSN-L)
- OpenAlex
- W2029884739
- Cited by
- 42
- References
- 0
- Citations by year
- 2026: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 2 · 2013: 3 · 2012: 3
- FWCI
- 0.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Shock (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Polyamine Metabolism and Applications
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Keywords
- spermine, polyamines, nitric oxide, lipopolysaccharide, endotoxemia, intestinal injury, inducible nitric oxide synthase, nitrotyrosine, TNF-α, macrophages, interferon-gamma, IL-10, systemic inflammation, sepsis, oral administration, intestinal mucosal integrity
- MeSH terms
- Administration, Oral, Animals, Disease Models, Animal, Escherichia coli, Female, Immunohistochemistry, Inflammation, Interferon-gamma, Intestinal Mucosa, Intestines, Lipopolysaccharides, Macrophages, Neutrophils, Nitrates, Nitric Oxide, Nitrites, Shock, Septic, Spermine, Tumor Necrosis Factor-alpha, Tyrosine, Interleukin-10, Nitric Oxide Synthase, Mice, Nitric Oxide Synthase Type II
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