Anti-LRAT (aa190-199) monoclonal antibody, clone N45Q2G20

Background: Chronic ethanol intake results in decreased hepatic vitamin A levels through both enhanced degradation of vitamin A via a cytochrome P450 enzyme (CYP)-dependent process and increased mobilization of vitamin A from the liver into the circulation. This study investigated whether treatment with chlormethiazole, a CYP inhibitor, restores vitamin A in the livers of ethanol-fed rats. Methods: Ethanol-exposed and non-ethanol-exposed rats were treated with or without chlormethiazole (10 and 100 mg/kg body weight) for 1 month. Liver and plasma levels of retinol and retinyl palmitate were analyzed by high-performance liquid chromatography. Expressions of hepatic lecithin: retinol acyltransferase (LRAT) and cellular retinol-binding protein were analyzed with reverse transcription-polymerase chain reaction. Hepatic retinol esterification by LRAT was examined by using incubations of the microsomal fractions of livers with exogenous sources of retinol. Results: Ethanol-feeding in rats for a month resulted in lower hepatic levels of retinol and retinyl palmitate than those found in controls and the occurrence of several polar retinoid metabolites. In contrast, treatment with chlormethiazole at two different doses in ethanol-fed rats completely blocked the formation of hepatic retinoid polar metabolites and restored hepatic levels of retinol and hepatic retinyl palmitate in a dose-dependent manner. Furthermore, increased plasma concentrations of retinyl palmitate in rats fed with ethanol, which indicate increased mobilization of vitamin A, were partially inhibited by chlormethiazole treatment. However, neither ethanol nor chlormethiazole treatment altered the expression and activity of LRAT in the liver of rats. Hepatic expression of cellular retinol-binding protein increased significantly in ethanol-fed rats with or without chlormethiazole treatment compared with control rats. Conclusions: These data suggest that chlormethiazole can restore both hepatic retinol and retinyl ester concentrations to normal levels in ethanol-fed rats through blocking enhanced both degradation of vitamin A and mobilization of vitamin A from the liver into the circulation.

In this study the accumulation of the 3,3'-dichlorobiphenyl (PCB-11) in monitoring organisms from the Antarctic and Mediterranean coastal environments has been investigated. This lesser-known PCB congener, unrelated to the industrial use of commercial mixtures, continues to be generated and released into the environment mainly as an unintentional by-product of pigment manufacturing. Specimens of the filter-feeders Adamussium colbecki from Terra Nova Bay and of Mytilus galloprovincialis and Ruditapes philippinarum from the north-western Adriatic coasts were collected and analyzed for PCB-11 by Gas Chromatography coupled both to Low-Resolution and High-Resolution Mass Spectrometry (LRMS, HRMS). In order to assess the influence of PCB-11 with respect to the legacy contamination, 126 PCB congeners related to the Aroclor commercial mixtures were simultaneously analyzed. PCB-11 was detected in all the samples, regardless of the species and of the geographical area, representing on average 17.6% and 15.6% of the total PCBs (n 127) in Antarctic and Mediterranean samples, respectively. In the Adriatic area the highest concentrations were related to the influence of industrial activities or ship traffic, while the highest value found in Antarctic specimens, namely those collected in the austral summer 1997-1998, was ascribed to a local anthropogenic source. The occurrence of PCB-11 in the other samples from Terra Nova Bay may be related to Long-Range Atmospheric Transport (LRAT), facilitated by the higher volatility of the analyte compared to the heavier PCB congeners. Nevertheless, more in-depth studies are needed in order to evaluate the relative contribution of local and distant sources.(C) 2017 Elsevier Ltd. All rights reserved.