An analytical survey of benzotriazole UV stabilizers in plastic products and their endocrine-disrupting potential via human estrogen and androgen receptors.

Benzotriazole UV stabilizers (BUVSs) are added to various materials to prevent damage from UV-irradiation. Recently, there has been great concern regarding the endocrine-disrupting effects of exposure to microplastic-derivative BUVSs in particular. In this study, we measured the concentrations of nine representative BUVSs in the plastic bottle caps of 10 beverages, 4 food packages, and 4 plastic shopping bags purchased from Japanese grocery stores by GC-MS analysis, and found that eight BUVSs, except for 2-(3,5-di-tert-butyl-2-hydroxyphenyl)-2H-benzotriazole (UV-320), were detected from these plastic products. In particular, 2-(2-hydroxy-5-methylphenyl) benzotriazole (UV-P) and 2-(2-hydroxy-3-tert-butyl-5-methylphenyl)-5-chlorobenzotriazole (UV-326) were detected from all the bottle caps at concentrations in the order of ng/g. In addition, we characterized the agonistic and/or antagonistic activities against human estrogen receptors (ERα/ß) and androgen receptor (AR) of 13 BUVSs. Results revealed that, among the 13 BUVSs, UV-P, 2-(5-tert-butyl-2-hydroxyphenyl) benzotriazole (UV-PS), 2-[2-hydroxy-5-[2-(methacryloyloxy)ethyl]phenyl]-2H-benzotriazole (UV-090) and 2-(2-hydroxy-5-tert-octylphenyl)-benzotriazole (UV-329) showed ERα and/or ERß agonistic activity, with UV-P being the most potent based on these assays. On the other hand, UV-320 and 2-(3-s-butyl-5-tert-butyl-2-hydroxyphenyl) benzotriazole (UV-350) showed both ERα and ERß antagonistic activities, and 2-(3,5-di-tert-amyl-2-hydroxylphenyl) benzotriazole (UV-328) and UV-329 acted as ERß antagonists. In the AR assay, UV-P and 2-(3-allyl-2-hydroxy-5-methylphenyl)-2H-benzotriazole (UV-9) showed AR antagonistic activity although none of the test compounds showed AR agonistic activity. Taken together, our findings suggest that a series of BUVSs are present in our environments via plastic materials and several of these compounds possess endocrine-disrupting potential, such as ERα/ß agonistic and/or antagonistic activity and AR antagonistic activity. UV-P and its structurally similar compounds, in particular, appear to be a cause for concern.

Method for approximating colloid osmotic pressure in long-term hemodialysis patients.

Colloid osmotic pressure (COP) is important in calculating vascular permeability during hemodialysis (HD). However, few reports have directly measured COP in HD patients. Therefore, the currently published formulas may not be clinically optimal for predicting COP for HD patients. Here, the study aims were (i) to directly measure COP in HD patients and compare the measured and predicted COP values using four previously reported formulas, and (ii) to develop a formula for approximating COP using clinical parameters. We obtained 212 measured COP values using an osmometer; the average value was 22.0 ± 0.2 mm Hg. The predicted COP based on the four different formulas was positively correlated with the measured COP (0.87 < r < 0.89), but was significantly overestimated compared to it (P < 0.001). We also performed a stepwise analysis using serum albumin and non-albumin protein concentrations and obtained the following simple formula for COP approximation: COP (mm Hg) = -7.91 + 5.64 × albumin (g/dL) + 3.00 × non-albumin proteins (g/dL). A positive linear correlation was observed between the measured COP and approximated COP using this formula (r = 0.90, P < 0.001). We calculated the mean Kr (plasma-refilling coefficient) as a marker for determining dry weight in HD patients using the measured COP and approximated COP. No differences were observed between the mean Kr derived from the measured and approximated COP. We report here significant differences between measured and predicted COP values, and have devised a simple formula for COP approximation in HD patients.

Glucocorticoid Generates ROS to Induce Oxidative Injury in the Hippocampus, Leading to Impairment of Cognitive Function of Rats.

The present study attempted to clarify whether over-secretion of glucocorticoids in the serum caused by increased hypothalamus-pituitary-adrenal activity induces oxidative stress in the rat brain, and how the stress causes the emergence of cognitive deficits. When rats were subcutaneously injected with corticosterone, lipid hydroperoxides and protein carbonyls increased markedly in the hippocampus in association with a decrease in activity of antioxidative enzymes, such as superoxide dismutase, catalase and glutathione peroxidase. These results suggest that high-level corticosterone in the serum induces reactive oxygen species (ROS), leading to oxidative damage in the hippocampus. After administration of corticosterone to rats, glucose and superoxide levels in the serum increased markedly. Furthermore, pyramidal cell apoptosis was observed to accompany the loss of glucocorticoid receptors at the cornus ammonis 1 region of the hippocampus. Rats injected with corticosterone showed marked deficits in memory function. The present results imply that ROS generated from the glycation reaction of increased glucose levels caused by gluconeogenesis activation through glucocorticoid with proteins in the serum attack the hippocampus to induce neurodegeneration, resulting in cognitive deficits in rats.