Prooxidant actions of bisphenol A (BPA) phenoxyl radicals: implications to BPA-related oxidative stress and toxicity

We investigated the prooxidant effects of bisphenol A (BPA) phenoxyl radicals in comparison with the phenoxyl radicals of 3-tert-butyl-4-hydroxyanisole (BHA), 2,6-di-tert-butyl-methylphenol (BHT) and 4-tert-butylphenol (TBP). The phenoxyl radicals, generated in situ by 1-electron oxidation of the corresponding phenol, were allowed to react with reduced nicotinamide adenine dinucleotide phosphate (NADPH) and rifampicin. The antioxidant activity of various phenols was examined based on the reduction of 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH). It was found that the prooxidant activity of BPA phenoxyl radicals far exceeded those of BHA and BHT of phenoxyl radicals. Unlike Trolox, BPA showed minimal DPPH scavenging activity. The strong prooxidant properties of BPA phenoxyl radicals propelled us to study the markers of cellular oxidative stress in GT1-7 hypothalamic neurons exposed to BPA. It was observed that neuronal cells exposed to BPA had increased generation of intracellular peroxides and mitochondrial superoxide (O-2(center dot-)). The formation of peroxides and O-2(center dot-) were time- and dose-dependent and that co-incubation with N-acetyl-L-cysteine or Trolox greatly lowered their levels. The results of the present study are consistent with emerging evidence that human populations (non-institutionalized) having higher levels of urinary BPA also have increased levels of oxidative stress markers and are prone to higher risk of cardiovascular diseases, diabetes and abnormalities in hepatic enzymes.