Short-term exposure of decabromodiphenyl ether in female adult Balb/c mice: Immune toxicity and self-recovery.

As a typical persistent organic pollutant, decabromodiphenyl ether (BDE-209) is associated with various health risks, especially on immune system, which is sensitive to environmental pollutants. In addition, there is a problem of multi-index estimation and lack of comprehensive evaluation in immune toxicity study. In this study, the immunotoxicity of BDE-209 was systematically estimated from the aspects of immunopathology, humoral immunity, cellular immunity and non-specific immunity, etc., and integrated biomarker responses (IBR) combined with principal component analysis was applied to comprehensively evaluate the immunotoxicity of BDE-209 and its self-recovery after discontinuation. Results showed that BDE-209 exposure could cause immunotoxicity. This response seems to depend on (1) atrophying immune organs (thymus and spleen), hepatomegaly accompanied by increasing aspartate aminotransferase and oxidative stress;(2) changing humoral (immunoglobulins) and cellular (lymphocyte proliferation and cytokine secretion) immunity indices; (3) altering related expressions of genes, and further leading to imbalance of Th1/Th2 (Th, helper T cell). Integrated biomarker responses (IBR) companied with principal component analysis selected five biomarkers (mRNA expression of GATA-3, malondialdehyde level in thymus, count of white blood cell, serum IgG and lipopolysaccharide-induced splenic lymphocyte proliferation) to clarify the immunotoxicity induced by BDE-209. Furthermore, IBR combined with factorial analysis revealed that the effect of BDE-209 could be dose-dependently reduced after withdrawal of BDE-209. Overall results suggested that BDE-209 has immunotoxicity on adult Balb/c mice, whereas this immunotoxicity could be reduced by the self-regulation of organisms to some extent.

Novel in situ visualisation of rat intestinal absorption of polyphenols via matrix-assisted laser desorption/ionisation mass spectrometry imaging.

Matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) is presently used in physiological evaluations for visualisation of targets in organs. In the present study, MALDI-MSI was used as a visualisation technique to investigate the intestinal absorption of polyphenols. Nifedipine/phytic acid-aided MALDI-MSI was performed to visualise theaflavin-3'-O-gallate (TF3'G) and epicatechin-3-O-gallate (ECG) in the rat jejunum for 50-µM, 60-min transport experiments. Non-absorbable TF3'G was successfully visualised at the apical region, whereas absorbable ECG was detected throughout the rat jejunum. MALDI-MSI was also performed to determine the transport routes of the target metabolites. Signals corresponding to TF3'G and ECG in the membranes were diminished following treatment with inhibitors targeting the monocarboxylic acid transporter and organic anion transporting polypeptides. Enhanced visualisation of TF3'G was achieved by inhibiting efflux routes. Our findings demonstrated that the present MALDI-MSI can provide critical spatial informations on intestinal absorption of targets, by which TF3'G and ECG were incorporated into intestinal tissues, followed by efflux back to the apical compartment. In addition, MALDI-MSI analyses suggested that TF3'G was resistant to phase II metabolism during the influx/efflux processes, whereas ECG was susceptible to methylation and sulphation reactions. In conclusion, inhibitor-aided MALDI-MSI could serve as a powerful in situ visualisation technique for verifying intestinal transport routes and investigating the metabolism of penetrants.