Efficacy of DL-alpha lipoic acid against systemic inflammation-induced mice: antioxidant defense system.

Inflammation can activate macrophages or monocytes and sequentially release several inflammatory cytokines and reactive oxygen species (ROS). Oxidative stress-induced acute inflammatory response plays an important role in several diseases. This study was designed to investigate the prophylactic effect of the antioxidant lipoic acid (LA) during inflammation-induced mice. Mice were divided in to three groups (n = 8 in each): control, systemic inflammation, and LA treated mice with systemic inflammation. Results show that ROS was significantly higher in lymphocytes, hepatocytes, and astrocytes (P < 0.05) of inflammation induced mice when compared with control but no significant changes were observed in the LA treated group. Increased levels of lipid peroxidation (LPO) and decreased activities of oxidants such as superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione, and ATPase were observed in the inflammation-induced mice, which returned to near normalcy following LA therapy. In vitro study has shown that LA treatment not only suppresses the increased LPO levels but also inhibits the lipid break down resulting from autoxidation. In addition, increased immunoreactivity of the astrocyte marker glial fibrillary acidic protein (GFAP) was observed in the neocortex region of inflammation-induced mice, whereas nuclear factor kappa B p65 (NFkappaB) immunoreactivity was observed in both the neocortex and liver of the same group which were effectively controlled by LA therapy suggesting that LA can efficiently manage systemic inflammation.

Molecular chaperone alpha-crystallin prevents detrimental effects of neuroinflammation.

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.