The arachidonic acid 5-lipoxygenase inhibitor nordihydroguaiaretic acid inhibits tumor necrosis factor alpha activation of microglia and extends survival of G93A-SOD1 transgenic mice.

Familial forms of amyotrophic lateral sclerosis (ALS) can be caused by mutations in copper, zinc-superoxide dismutase (SOD1). Mice expressing SOD1 mutants demonstrate a robust neuroinflammatory reaction characterized, in part, by up-regulation of tumor necrosis factor alpha (TNFalpha) and its primary receptor TNF-RI. In an effort to identify small molecule inhibitors of neuroinflammation useful in treatment of ALS, a microglial culture system was established to identify TNFalpha antagonists.

Anti-inflammatory effects of tocopherol metabolites.

Our objective was to assess the anti-inflammatory effects of alpha-tocopherol, gamma-tocopherol, and their metabolites 2,5,7,8-tetramethyl-2-(beta-carboxyethyl)-6-hydroxychroman (alpha-CEHC) and 2,7,8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman (gamma-CEHC) in defined cell culture systems. Rat aortic endothelial cells and mouse microglial cultures were treated with tumor necrosis factor TNFalpha or bacterial lipopolysaccharide (LPS) and nitrite and prostaglandin E(2) (PGE(2)) were measured. alpha-CEHC suppressed TNFalpha-stimulated nitrite production in both cell types, whereas both CEHC derivatives inhibited LPS-stimulated microglial nitrite efflux.

New perspectives on vitamin E: gamma-tocopherol and carboxyelthylhydroxychroman metabolites in biology and medicine.

Vitamin E (alpha-tocopherol or alphaT) has long been recognized as a classic free radical scavenging antioxidant whose deficiency impairs mammalian fertility. In actuality, alpha-tocopherol is one member of a class of phytochemicals that are distinguished by varying methylation of a chroman head group. Early studies conducted between 1922 and 1950 indicated that alpha-tocopherol was specific among the tocopherols in allowing fertility of laboratory animals.

Oxidized LDLs affect nitric oxide and radical generation in brain endothelial cells.

There is an increase in the generation of reactive oxygen species and nitric oxide in the cerebral microcirculation in Alzheimer's disease. The factors that cause this increase in oxidative stress have not been identified. Increasing evidence suggests that there are common mechanisms in atherosclerosis and Alzheimer's disease.

Message and protein-level elevation of tumor necrosis factor alpha (TNF alpha) and TNF alpha-modulating cytokines in spinal cords of the G93A-SOD1 mouse model for amyotrophic lateral sclerosis.

Recent data indicate that certain pro-inflammatory cytokines are transcriptionally upregulated in the spinal cords of G93A-SOD1 mice, a model of amyotrophic lateral sclerosis (ALS). We previously showed that the receptor for tumor necrosis factor alpha (TNF-R1) was notably elevated at late presymptomatic as well as symptomatic phases of disease (J. Neurochem.