Significant In Vivo Anti-Inflammatory Activity of Pytren4Q-Mn a Superoxide Dismutase 2 (SOD2) Mimetic Scorpiand-Like Mn (II) Complex

Abstract

BackgroundThe 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.Background/MethodologyWe have recently reported that two SOD mimetic compounds, the MnII 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 MnII 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.Principal FindingsIn this report we show that the MnII 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.Conclusion/SignificanceThe effective anti-inflammatory activity of the MnII 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.

Mechanisms of TQ-6, a Novel Ruthenium-Derivative Compound, against Lipopolysaccharide-Induced In Vitro Macrophage Activation and Liver Injury in Experimental Mice: The Crucial Role of p38 MAPK and NF-κB Signaling

“…Moreover, it has been recognized that MAPKs play a pivotal role in the pathogenesis of many inflammatory disorders [ 27 ]. A study demonstrated that manganese (II) complex diminishes the gene expression and protein secretion of cytokines induced by LPS in THP-1 macrophages, probably due in part to the inactivation of the MAPK signaling pathway [ 28 ]. Recent in vitro studies in RAW 264.7 cells have shown that p38 MAPK is involved in NF-κB activation [ 29 ], and our data also proved this hypothesis in that the p38 inhibitor, SB203508, inhibited p65.…”

Adipose tissue glycogen accumulation is associated with obesity-linked inflammation in humans

“…The SGBS cell line, provided by Dr. Wabitsch (University of Ulm, Germany) and Lisa-2 cells, provided by Dr. Möller (University of Ulm, Germany), were used as cellular models of human subcutaneous and visceral pre-adipocytes, respectively, and were induced to differentiate as described [17] . THP-1 cells (a human monocytic cell line; ATCC, Rockville, MD) were induced to differentiate to macrophages with PMA as previously described [18] . The human myogenic cell line LHCN-M2 was used as a cellular model of human myoblasts.…”

Sensing Zn2+ in Aqueous Solution with a Fluorescent Scorpiand Macrocyclic Ligand Decorated with an Anthracene Bearing Tail

“…Scorpiand type aza-macrocyclic ligands, that is aza-macrocyclic ligands with coordinating tails [1], and their metal complexes have attracted considerable interest thanks to the numerous uses they have been tested for, including but not limited to various biomedical applications [2,3] (MRI contrast agents [4,5], radioisotopes complexation and radiolabelling [6][7][8][9], radiotherapy [10][11][12][13][14], chelation therapy [15][16][17], antiproliferative treatments [18][19][20][21], enzyme mimicking [22][23][24][25][26][27][28][29]), catalysis [30][31][32][33][34][35][36] and chemosensing [37][38][39][40][41][42][43].…”