Aim: 

Oxidative stress and inflammation have been implicated in neurodegenerative disorders such as Alzheimer's disease (AD) and it is desirable to find methods of tipping the balance towards an anti-inflammatory state and compounds to prevent oxidative stress. Oestrogenic compounds have various effects, including anti-inflammatory and antioxidant activity.

Methods: 

Cells were pretreated with 17-b-estradiol (0.2 nM) or with genistein (0.5 mM), and 48 h later treated with 5 mM of amyloid beta (Ab) for 24 h.

Results: 

We found that Ab increased oxidative stress, measured as peroxide and malondialdehyde (MDA) levels and induced inflammatory mediators, such as cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin 1b (IL-1b) and tumor necrosis factor a (TNF-a). All these effects were prevented when cells were pretreated for 48 h with oestradiol or genistein, demonstrating antioxidant and anti-inflammatory effects of oestradiol or genistein in astrocytes in primary culture. The Ab-stimulated expression of proinflammatory genes in cells is antagonized by the action of the PPAR receptors (Peroxisome-proliferator activated receptors). Here we detected an increase in PPAR-g expression in cells treated with Ab and a major induction was observed when the oestradiol or soy isoflavone genistein were used to treat cells.

Conclusion: 

Oestrogenic compounds have antioxidant and anti-inflammatory effects and activate PPAR receptors suppressing a diverse array of inflammatory responses caused by Ab in astrocytes in primary culture.