Agmatine Mitigates Inflammation-Related Oxidative Stress in BV-2 Cells by Inducing a Pre-Adaptive Response

• Published in: International journal of molecular sciences 2022-03, Vol.23 (7), p.3561
• Main Authors: Milosevic, Katarina, Stevanovic, Ivana, Bozic, Iva D, Milosevic, Ana, Janjic, Marija M, Laketa, Danijela, Bjelobaba, Ivana, Lavrnja, Irena, Savic, Danijela
• Format: Article
• Language: English
• Subjects: Agmatine; Agmatine - metabolism; Agmatine - pharmacology; Alzheimer's disease; Animals; Antioxidants; Cyclooxygenase-2; Cytokines; Enzymes; Gene expression; Genotype & phenotype; Glutathione - metabolism; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Interleukin 1; Interleukin 6; Kinases; Lipid peroxidation; Lipids; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Mice; Microglia; Microglia - metabolism; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; NF-κB protein; Nitric-oxide synthase; Oxidative Stress; Phenotypes; Proteins; Tumor necrosis factor
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23073561

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 O 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.