Significant in vivo anti-inflammatory activity of Pytren4Q-Mn a superoxide dismutase 2 (SOD2) mimetic scorpiand-like Mn (II) complex

• Published in: PloS one 2015-03, Vol.10 (3), p.e0119102
• Main Authors: Serena, Carolina, Calvo, Enrique, Clares, Mari Paz, Diaz, María Luisa, Chicote, Javier U, Beltrán-Debon, Raúl, Fontova, Ramón, Rodriguez, Alejandro, García-España, Enrique, García-España, Antonio
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Anti-inflammatory agents; Anti-Inflammatory Agents - pharmacology; Antioxidants; Arthritis; Atherosclerosis; Bacteria; Biocompatibility; Cell Line; Cercopithecus aethiops; Diabetes; Enzymes; Humans; Immunogenicity; Immunology; Inflammation; Isomers; Kinases; Lipopolysaccharides; Low molecular weights; Macrophages; Male; Manganese - metabolism; MAP Kinase Signaling System; Medical research; Metabolism; Mice; Mimetic compounds; Molecular Mimicry; Molecular modelling; Molecular structure; Molecular weight; Nitric oxide; Observations; Penicillin; Pharmacology; Polyamines; Precision medicine; Properties; Sepsis; Solubility; Superoxide dismutase; Superoxide Dismutase - metabolism; Toxicity; Vero Cells; Water pollution effects; Yeast
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0119102

The clinical use of purified SOD enzymes has strong limitations due to their large molecular size, high production cost and immunogenicity. These limitations could be compensated by using instead synthetic SOD mimetic compounds of low molecular weight. We have recently reported that two SOD mimetic compounds, the Mn(II) complexes of the polyamines Pytren2Q and Pytren4Q, displayed high antioxidant activity in bacteria and yeast. Since frequently molecules with antioxidant properties or free-radical scavengers also have anti-inflammatory properties we have assessed the anti-inflammatory potential of Pytren2Q and Pytren4Q Mn(II) complexes, in cultured macrophages and in a murine model of inflammation, by measuring the degree of protection they could provide against the cellular injury produced by lipopolisacharide, a bacterial endotoxin. In this report we show that the Mn(II) complex of Pytren4Q but not that of Pytren2Q effectively protected human cultured THP-1 macrophages and whole mice from the inflammatory effects produced by LPS. These results obtained with two molecules that are isomers highlight the importance of gathering experimental data from animal models of disease in assessing the potential of candidate molecules. The effective anti-inflammatory activity of the Mn(II) complex of Pytren4Q in addition to its low toxicity, water solubility and ease of production would suggest it is worth taking into consideration for future pharmacological studies.