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Agmatine Mitigates Inflammation-Related Oxidative Stress in BV-2 Cells by Inducing a Pre-Adaptive Response
Katarina Milosevic1, Ivana Stevanovic2, Iva D Bozic1
1Institute for Biological Research "Siniša Stanković"-National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia.
Abstract:
Neuroinflammation and microglial activation, common components of most neurodegenerative diseases, can be imitated in vitro by challenging microglia cells with Lps. We here aimed to evaluate the effects of agmatine pretreatment on Lps-induced oxidative stress in a mouse microglial BV-2 cell line. Our findings show that agmatine suppresses nitrosative and oxidative burst in Lps-stimulated microglia by reducing iNOS and XO activity and decreasing O2- levels, arresting lipid peroxidation, increasing total glutathione content, and preserving GR and CAT activity. In accordance with these results, agmatine suppresses inflammatory NF-kB, and stimulates antioxidant Nrf2 pathway, resulting in decreased TNF, IL-1 beta, and IL-6 release, and reduced iNOS and COX-2 levels. Together with increased ARG1, CD206 and HO-1 levels, our results imply that, in inflammatory conditions, agmatine pushes microglia towards an anti-inflammatory phenotype. Interestingly, we also discovered that agmatine alone increases lipid peroxidation end product levels, induces Nrf2 activation, increases total glutathione content, and GPx activity. Thus, we hypothesize that some of the effects of agmatine, observed in activated microglia, may be mediated by induced oxidative stress and adaptive response, prior to Lps stimulation.
Insights
Agmatine pretreatment reduces oxidative stress and inflammation in LPS-stimulated microglia. It also promotes an anti-inflammatory microglial phenotype, suggesting therapeutic potential for neurodegenerative diseases.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Neuroinflammation and microglial activation are hallmarks of neurodegenerative diseases.
- Lipopolysaccharide (LPS) is used to induce inflammatory and oxidative stress in microglial cell models.
- Agmatine's potential effects on neuroinflammation require further investigation.
Purpose of the Study:
- To evaluate the protective effects of agmatine pretreatment against LPS-induced oxidative stress and inflammation in a mouse microglial BV-2 cell line.
- To elucidate the molecular mechanisms underlying agmatine's action on microglial activation.
Main Methods:
- BV-2 microglial cells were pretreated with agmatine followed by LPS stimulation.
- Assessed levels of oxidative stress markers (e.g., O2-, lipid peroxidation, glutathione).
- Measured activity of key enzymes (e.g., iNOS, XO, GR, CAT, GPx).
- Analyzed inflammatory markers (e.g., TNF, IL-1β, IL-6) and transcription factors (NF-κB, Nrf2).
- Quantified microglial phenotype markers (e.g., ARG1, CD206, HO-1).
Main Results:
- Agmatine pretreatment significantly suppressed LPS-induced oxidative and nitrosative stress.
- Agmatine reduced pro-inflammatory mediators (TNF, IL-1β, IL-6) and inflammatory markers (iNOS, COX-2).
- Agmatine promoted an anti-inflammatory microglial phenotype by increasing ARG1, CD206, and HO-1.
- Agmatine alone induced adaptive responses, including Nrf2 activation and increased glutathione, suggesting a hormetic effect.
Conclusions:
- Agmatine exerts significant anti-inflammatory and antioxidant effects in LPS-activated microglia.
- Agmatine modulates microglial phenotype towards an anti-inflammatory state.
- Agmatine's protective mechanisms may involve pre-conditioning via mild oxidative stress induction.
