The effects of fatty acids and antioxidants on U937 monocytes used as a model for the lipid disturbance in schizophrenia

Obajimi, Oluwakemi (2003). The effects of fatty acids and antioxidants on U937 monocytes used as a model for the lipid disturbance in schizophrenia. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0000f57a

Abstract

Schizophrenia is a devastating mental disease affecting approximately 1% of all populations. Recent studies have suggested that deficient uptake of free fatty acids or excessive breakdown of cell-membrane phospholipids, directly or indirectly triggered by lipid peroxidative damage, may be associated with schizophrenia and possibly other neurodegenerative disorders.

This study provides more information on the influence of the presence of different fatty acids (FAs): stearic acid (SA), oleic acid (OA), arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) and dietary antioxidants (ascorbic acid, atocopherol, f3-carotene and astaxanthin) as components of the culture-medium on the human monocytic cell line (U937) by the measurements of cell-viability, productions of by-products of lipid peroxidation (lipid hydroperoxides and volatile hydrocarbons), AA release/uptake and cPLA2 expression upon induced-oxidative stress with the radical mediating system oft-butyl hydroperoxide (t-BHP)/Fe²⁺.

Of all FAs used, the PUFAs (AA, EPA and DHA) at 40 µM concentrations reduced cell membrane integrity significantly whereas SA and OA had no effect after 72 h of incubation, suggesting the cytotoxicity of the PUF As above certain concentrations.

This study shows that U937 cells accumulate lipid hydroperoxides, generate ethane, butane and pentane, release and incorporate AA at a greater rate in response to induced-oxidative stress by a mechanism probably involving cPLA₂. In addition, AA is incorporated into cellular phospholipids at a greater rate post-oxidation. With oxidative-stress, the presence of EPA but not DHA in cellular phospholipids significantly increases the accumulation of AA in the extracellular fluid.

Studies revealed that under oxidative-stress α-tocopherol is a potent antioxidant markedly inhibiting AA-release but not its uptake. Whilst ascorbic acid appeared to promote AA release, β-carotene and astaxanthin conferred no protective effect. Collectively, this study demonstrates the potency of α-tocopherol, ascorbic acid, β-carotene and astaxanthin against oxidant-induced peroxidative damage, AA release/uptake and ultimately total loss of cell-viability. In EPA-pretreated cells, AA-release is enhanced with/without oxidant activation suggesting its action by stimulating the availability of AA possibly for prostaglandin production.