Characterization of novel furan compounds on the basis of their radical scavenging activity and cytoprotective effects against glutamate- and lipopolysaccharide-induced insults

There is increasing evidence indicating that free radicals and oxygenases such as cyclooxygenase (COX) and lipoxygenase (LOX) are related to the onset and development of neurodegenerative diseases. In order to prevent and/or delay these diseases, the use of radical-scavenging antioxidants and inhibitors against oxygenases has received much attention. In the present study, we examined the radical-scavenging activity and cytoprotective effects of some novel furan compounds with potent inhibitory activity against oxygenases such as COX-1, COX-2, and 5-LOX. The radical-scavenging activity was assessed by studying the bleaching of beta-carotene by free radicals generated from an azo initiator. In this assay system, the rate constants for scavenging peroxyl radicals by furan S and furan L was estimated to be 2 x 10(4) and 3 x 10(4) M(-1) s(-1), respectively. We also investigated the cytoprotective effects of these compounds against cell death induced by several toxins. We found that the furan compounds exhibited cytoprotective effects against PC12 cell death induced by linoleic acid hydroperoxide, primary neuronal cell death induced by glutamate, and cell death induced by lipopolysaccharide. These results suggest the beneficial effects of the furan compounds against disorders related to glutamate and lipopolysaccharide.     

Antioxidant capacity of BO-653, 2,3-dihydro-5-hydroxy-4,6-di-tert-butyl-2,2-dipentylbenzofuran, and uric acid as evaluated by ORAC method and inhibition of lipid peroxidation

The role of radical-scavenging antioxidant against oxidative stress has received much attention. The antioxidant capacity has been assessed by various methods. Above all, oxygen radical absorbance capacity (ORAC) has been frequently employed [Prior et.al., J. Agric. Food Chem.2005, 53, 4290]. In the present study, the antioxidant capacity of 2,3-dihydro-5-hydroxy-4,6-di-tert-butyl-2,2-dipentylbenzofuran (BO-653) and uric acid was assessed by ORAC method using pyranine as a reference probe and compared with that against lipid peroxidation of human plasma. It was found that BO-653 was assessed to be much less potent than uric acid by ORAC method, whereas BO-653 exerted much higher antioxidant activity than uric acid against plasma lipid peroxidation. The reason for such discrepancy is discussed. The results suggest that ORAC method is suitable for the assessment of free radical scavenging capacity, but not for the assessment of antioxidant capacity against lipid peroxidation in plasma.