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.

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During the course of cancer radiation treatment, normal skin invariably suffers from the cytotoxic effects of gamma-radiation and reactive oxygen species (ROS), which are generated from the interaction between radiation and the water molecules in cells. The present study was designed to investigate the radioprotective role of alpha-lipoic acid (LA), an antioxidant on murine skin fibroblasts exposed to a single dose of 2, 4, 6, or 8Gy gamma-radiation. Irradiation of fibroblasts significantly increased ROS, nitric oxide, and lipid peroxidation (P < 0.001); all of these factors substantially decreased with 100 microM LA treatment. Hydroxyl radical (OH(.)) production from 8Gy irradiated fibroblasts was measured directly by electron spin resonance using spin-trapping techniques. LA was found to inhibit OH(.) production at 100-microM concentrations. Dose-dependent depletion of antioxidants, such as catalase and glutathione reductase, was observed in irradiated fibroblasts (P < 0.001), along with increased superoxide dismutase (P < 0.001). LA treatment restored antioxidant levels. Concentration of the pro-inflammatory cytokine IL-1beta was significantly reduced in irradiated fibroblasts when treated with LA. MTT and lactate dehydrogenase assays demonstrated that LA treatment reduced cell injury and protected cells against irradiation-induced cytotoxicity. Thus, we conclude that results are encouraging and need further experiments to demonstrate a possible benefit in cancer patients and the reduction of harmful effects of radiation therapy.

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