Equol Effectively Inhibits Toxic Activity of Human Neutrophils without Influencing Their Viability.

Equol (7,4'-dihydroxy-isoflavan, or 4',7-isoflavandiol) is a chroman derivative produced by intestinal bacteria in response to soy isoflavone intake in some, but not in all, humans. Equol shows strong anti-oxidant, anti-estrogenic, anti-cancerous and anti-inflammatory properties. The antioxidative capacity of equol has recently received considerable attention, and it has been used for preventing and treating several diseases. We investigated the effect of equol on human neutrophils, extra- and intracellular formation of oxidants, the phosphorylation of protein regulating NADPH oxidase and its effect on apoptosis. Neutrophils, isolated from blood from healthy subjects, were tested upon activation with various stimulants, proper for reactive oxygen species (ROS) production and treated by equol. Equol has the ability to reduce the toxic action of neutrophils. With increasing concentrations, equol decreased the amount of oxidants produced by neutrophils both extra- and intracellularly. The phosphorylation of p40(phox) (a component of NADPH oxidase, responsible for the assembly of functional oxidase in intracellular membranes) was reduced in the presence of equol. The experiments showed that equol did not change the number of viable, apoptotic or dead neutrophils significantly in all concentrations used. These results indicate the promising effect of equol in the operation of ROS in different mechanisms in the model of inflammation.

Selective inhibition of extracellular oxidants liberated from human neutrophils--A new mechanism potentially involved in the anti-inflammatory activity of hydroxychloroquine.

Hydroxychloroquine is used in the therapy of rheumatoid arthritis or lupus erythematosus. Although these diseases are often accompanied by activation of neutrophils, there are still few data relating to the impact of hydroxychloroquine on these cells. We investigated the effect of orally administered hydroxychloroquine on neutrophil oxidative burst in rats with adjuvant arthritis. In human neutrophils, extra- and intracellular formation of oxidants, mobilisation of intracellular calcium and the phosphorylation of proteins regulating NADPH oxidase assembly were analysed. Administration of hydroxychloroquine decreased the concentration of oxidants in blood of arthritic rats. The inhibition was comparable with the reference drug methotrexate, yet it was not accompanied by a reduction in neutrophil count. When both drugs were co-applied, the effect became more pronounced. In isolated human neutrophils, treatment with hydroxychloroquine resulted in reduced mobilisation of intracellular calcium, diminished concentration of external oxidants and in decreased phosphorylation of Ca(2+)-dependent protein kinase C isoforms PKCα and PKCßII, which regulate activation of NADPH oxidase on plasma membrane. On the other hand, no reduction was observed in intracellular oxidants or in the phosphorylation of p40(phox) and PKCδ, two proteins directing the oxidase assembly to intracellular membranes. Hydroxychloroquine reduced neutrophil-derived oxidants potentially involved in tissue damage and protected those capable to suppress inflammation. The observed effects may represent a new mechanism involved in the anti-inflammatory activity of this drug.

Dermal absorption and hydrolysis of methylparaben in different vehicles through intact and damaged skin: using a pig-ear model in vitro.

Currently, there is a trend to reduce of parabens use due to concern about the safety of their unmetabolised forms. This paper focused on dermal absorption rate and effectiveness of first-pass biotransformation of methylparaben (MP) under in-use conditions of skincare products. 24-h exposure of previously frozen intact and tapestripped (20 strips) pig-ear skin to nine vehicles containing 0.1% MP (AD, applied dose of 10 µg/cm²), resulted in 2.0-5.8%AD and 2.9-7.6%AD of unmetabolised MP, and 37.0-73.0%AD and 56.0-95.0%AD of p-hydroxybenzoic acid, respectively, in the receptor fluid. The absorption rate of MP was higher from emulsions than from hydrogels, from enhancer-containing vehicles than from enhancer-free vehicles, and when skin was damaged. Experiments confirmed that the freezing of pig-ear skin slightly reduces hydrolysis of MP. After 4-h exposure of intact freshly excised and intact frozen stored skin, amount of

Absorption of triphenylmethane dyes Brilliant Blue and Patent Blue through intact skin, shaven skin and lingual mucosa from daily life products.

Currently, there is evidence of health risks of triphenylmethane dyes after systemic absorption. This paper investigates the fate of Brilliant Blue (BB) and Patent Blue (PB) after 24-h in vitro diffusion, firstly through intact and secondly through shaven pig-ear skin (stored by freezing) from four leave-on cosmetics under in-use conditions. Both dyes showed no measurable permeation through intact skin but significant permeation was found through shaven skin. From 250 ng/cm(2) of dye in one applied dose there were found 52 ng/cm(2) of BB and 91 ng/cm(2) of PB from ethanol-based after-shave, 39 ng/cm(2) of BB and 86 ng/cm(2) of PB from ethanol-free facial-cleanser, 35 ng/cm(2) of BB and 43 ng/cm(2) of PB from O/W emulsion, and no amount from W/O emulsion, as available to become systemically absorbed. Thirdly, the paper focuses on lingual mucosa after licking lollipops. Ex vivo porcine tongue dorsum was exposed to human saliva with 15,000 ng/cm(2) of dye for 20 min. 24-h diffusion resulted in 34 ng/cm(2) of BB and 86 ng/cm(2) of PB which can be directly absorbed into the blood system. Findings are troubling, particularly with regard to the frequent use of after-shave products by the male population and repeated lollipops licking by children.