2-2-dimethyl-5-hydroxy-1-pyrrolidinyloxy and Inflammation

In recent years spin trapping techniques have been used extensively to better understand the free radical biology of phagocytic cells. These results demonstrate that spin trapping is of adequate sensitivity to detect superoxide and/or hydroxyl radical generated by these cells, and that spin trapping is capable of measuring phagosomal radicals as well. However, neither neutrophils, monocytes, nor monocyte derived macrophages generate hydroxyl radical in the absence of exogenous iron. Furthermore, neutrophil lactoferrin and myeloperoxidase limit the magnitude (and in the case of lactoferrin the duration) of hydroxyl radical formed by neutrophils in an iron catalyzed system. Since monocytic phagocytes possess no lactoferrin, and limited myeloperoxidase, hydroxyl radical may play an important role in the inflammatory behavior of mononuclear phagocytes.

Topics: Cyclic N-Oxides; Free Radicals; Humans; Hydroxides; Hydroxyl Radical; Inflammation; Lysosomes; Phagocytes; Phagocytosis; Spin Labels; Superoxide Dismutase

Silver nitrate administration stimulates immune activation, inflammation and deterioration in cell function. It is well established that hippocampal and cortical tissue are susceptible to degeneration in responses to insult such as oxidative stress or infection. This study was designed to investigate the prophylactic effect of alpha-crystallin, a major chaperone lens protein comprising of alpha-A and alpha-B subunits in inflammation induced mice. Mice were divided into three groups (n=6 in each), control, inflammation and alpha-crystallin treated. Our result shows that alpha-crystallin pretreatment effectively diminished systemic inflammation induced glial fibrillary acidic protein (GFAP) and nuclear factor kappa B (NFkappaB) expression in the mice neocortex, reversed elevated intracellular calcium levels, acetylcholine esterase activity and depletion of glucose. Furthermore it also significantly prevented nitric oxide (P<0.05) and lipid peroxide production in the plasma, liver, neocortex and hippocampus of the inflammation-induced mice. In order to demonstrate the direct *OH and nitric oxide radical scavenging ability of alpha-crystallin, an In vitro experiment using primary astrocyte culture subjected to lipopolysaccharide (LPS), a well-known inflammatory stimuli were also carried out. This study reiterates that alpha-crystallin therapy may serve as a potent pharmacological agent in neuroinflammation.

Topics: Acetylcholine; Acetylcholinesterase; alpha-Crystallins; Animals; Astrocytes; Calcium; Cattle; Cells, Cultured; Cyclic N-Oxides; Glial Fibrillary Acidic Protein; Glucose; Hepatocytes; Inflammation; Lymphocytes; Male; Mice; Neuroprotective Agents; NF-kappa B; Nitric Oxide; Silver Nitrate; Spin Labels