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


RESULTS
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.


CONCLUSIONS
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.
Research Unit, Hospital Joan XXIII, Institut d'Investigació Sanitaria Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain.
Carolina
C
Serena
Research Unit, Hospital Joan XXIII, Institut d'Investigació Sanitaria Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain.
Enrique
E
Calvo
Instituto de Ciencia Molecular, Departamento de Química Inorgánica, Universidad de Valencia, Valencia, Spain.
Mari Paz
MP
Clares
Pathology Department, Hospital Joan XXIII, Institut d'Investigació Sanitaria Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain.
María Luisa
ML
Diaz
Research Unit, Hospital Joan XXIII, Institut d'Investigació Sanitaria Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain.
Javier U
JU
Chicote
Research Unit, Hospital Joan XXIII, Institut d'Investigació Sanitaria Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain.
Raúl
R
Beltrán-Debon
Rheumatology Department, Hospital Joan XXIII, Institut d'Investigació Sanitaria Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain.
Ramón
R
Fontova
Critical Care Department, Hospital Joan XXIII, Institut d'Investigació Sanitaria Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain; CIBER de enfermedades respiratorias (CIBERES), ISC III, Bunyola, Palma de Mallorca, Spain.
Alejandro
A
Rodriguez
Instituto de Ciencia Molecular, Departamento de Química Inorgánica, Universidad de Valencia, Valencia, Spain.
Enrique
E
García-España
Research Unit, Hospital Joan XXIII, Institut d'Investigació Sanitaria Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain.
Antonio
A
García-España
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D008345:Manganese / Q000378:metabolism*; D051379:Mice; D018716:Molecular Mimicry; D013482:Superoxide Dismutase / Q000378:metabolism*; D014709:Vero Cells
D000893:Anti-Inflammatory Agents; D008345:Manganese; D013482:Superoxide Dismutase