Orally available Mn porphyrins with superoxide dismutase and catalase activities.

Superoxide dismutase/catalase mimetics, such as salen Mn complexes and certain metalloporphyrins, catalytically neutralize reactive oxygen and nitrogen species, which have been implicated in the pathogenesis of many serious diseases. Both classes of mimetic are protective in animal models of oxidative stress. However, only AEOL11207 and EUK-418, two uncharged Mn porphyrins, have been shown to be orally bioavailable.

Prolongation of alloskin graft survival by catalytic scavengers of reactive oxygen species.

We tested the effects of salen manganese (Salen-Mn) complexes, which are scavengers of reactive oxygen species exhibiting superoxide dismutase and catalase activities on the rejection of and alloresponse to fully allogeneic skin grafts in mice. We showed that pre-transplant treatment of C57Bl/6 donor skin or of BALB/c recipients with Salen-Mn complexes significantly delayed allograft rejection. ELISPOT analysis of alloimmune response of treated mice revealed a significant reduction of the frequency of type 1 cytokine (pro-inflammatory) producing T-cells, while the number of activated T-cells producing type 2 cytokines was elevated.

Oxidative neuropathology and putative chemical entities for Alzheimer's disease: neuroprotective effects of salen-manganese catalytic anti-oxidants.

Considerable evidence exists that the brains of individuals with Alzheimer's disease are subject to elevated levels of oxidative stress, particularly in regions exhibiting pathological damage. A major contributor to this oxidative stress appears to be the inflammatory process. Activation of rodent microglial cells by LPS or beta-amyloid peptide results in a marked up-regulation of inducible nitric oxide synthase (iNOS) and corresponding nitric oxide (NO) production.

Reversal of age-related learning deficits and brain oxidative stress in mice with superoxide dismutase/catalase mimetics.

Oxidative stress has been implicated in cognitive impairment in both old experimental animals and aged humans. This implication has led to the notion that antioxidant defense mechanisms in the brain are not sufficient to prevent age-related increase in oxidative damage and that dietary intake of a variety of antioxidants might be beneficial for preserving brain function. Here we report a dramatic loss of learning and memory function from 8 to 11 months of age in mice, associated with marked increases in several markers of brain oxidative stress.

Salen-manganese complexes as catalytic scavengers of hydrogen peroxide and cytoprotective agents: structure-activity relationship studies.

Synthetic catalytic scavengers of reactive oxygen species (ROS) may have broad clinical applicability. In previous papers, two salen-manganese complexes, EUK-8 and EUK-134, had superoxide dismutase (SOD) and catalase activities and prevented ROS-associated tissue injury. This study describes two series of salen-manganese complexes, comparing catalytic ROS scavenging properties and cytoprotective activities.