Organic anion-transporting polypeptides (OATPs) are multispecific transporters mediating the uptake of endogenous compounds and xenobiotics in tissues that are important for drug absorption and elimination, including the intestine and liver. Silymarin is a popular herbal supplement often used by patients with chronic liver disease; higher oral doses than those customarily used (140 mg three times/ day) are being evaluated clinically. The present study examined the effect of silymarin flavonolignans on OATP1B1-, OATP1B3-, and OATP2B1-mediated transport in cell lines stably expressing these transporters and in human hepatocytes. In overexpressing cell lines, OATP1B1-and OATP1B3-mediated estradiol-17b-glucuronide uptake and OATP2B1-mediated estrone-3-sulfate uptake were inhibited by most of the silymarin flavonolignans investigated. OATP1B1-, OATP1B3-, and OATP2B1-mediated substrate transport was inhibited efficiently by silymarin (IC 50 values of 1.3, 2.2 and 0.3 mM, respectively), silybin A (IC 50 values of 9.7, 2.7 and 4.5 mM, respectively), silybin B (IC 50 values of 8.5, 5.0 and 0.8 mM, respectively), and silychristin (IC 50 values of 9.0, 36.4, and 3.6 mM, respectively). Furthermore, silymarin, silybin A, and silybin B (100 mM) significantly inhibited OATP-mediated estradiol-17b-glucuronide and rosuvastatin uptake into human hepatocytes. Calculation of the maximal unbound portal vein concentrations/IC 50 values indicated a low risk for silymarin-drug interactions in hepatic uptake with a customary silymarin dose. The extent of silymarin-drug interactions depends on OATP isoform specificity and concentrations of flavonolignans at the site of drug transport. Higher than customary doses of silymarin, or formulations with improved bioavailability, may increase the risk of flavonolignan interactions with OATP substrates in patients.

Cadmium (Cd) is carcinogenic to humans and can accumulate in the liver, kidneys, and bones. There is widespread presence of cadmium in the environment as a consequence of anthropogenic activities. It is important to detect cadmium in the environment to prevent further exposure to humans. Previous whole-cell biosensor designs were focused on single-sensing constructs but have had difficulty in distinguishing cadmium from other metal ions such as lead (Pb) and mercury (Hg). We developed a dual-sensing bacterial bioreporter system to detect bioavailable cadmium by employing CadC and CadR as separate metal sensory elements and eGFP and mCherry as fluorescent reporters in one genetic construct. The capability of this dual-sensing biosensor was proved to simultaneously detect bioavailable cadmium and its toxic effects using two sets of sensing systems while still maintaining similar specificity and sensitivity of respective signal-sensing biosensors. The productions of double-color fluorescence were directly proportional to the exposure concentration of cadmium, thereby serving as an effective quantitative biosensor to detect bioavailable cadmium. This novel dual-sensing biosensor was then validated to respond to Cd(II) spiked in environmental water samples. This is the first report of the development of a novel dual-sensing, whole-cell biosensor for simultaneous detection of bioavailable cadmium. The application of two biosensing modules provides versatile biosensing signals and improved performance that can make a significant impact on monitoring high concentration of bioavailable Cd(II) in environmental water to reduce human exposure to the harmful effects of cadmium.

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Metal distributions were monitored along soil profiles and their sources as well as ecological risks were assessed in tidal zone (T), petroleum exploitation zone (P) and restoration zone (R) under different vegetation covers-Phragmites australis (p), Suaeda salsa (s) and bare land (b) in Yellow River estuary (YRE). In the three zones, mean concentrations of metals and mean values of potential ecological risk index (RI) kept the order of P>T>R. For different vegetation covers, the order of mean concentrations and ecological risk factor of all metals was b>s>p in zone P, while it shifted to p>b>s in zone T and p>s>b in zone R, respectively. Principal component analysis inferred that As, Cu, Ni and Zn were derived from natural alluviation and sedimentation, while Cd and Pb were derived from allochthonous inputs and air emissions of oil extraction. Correlation analysis indicated that soil organic matter, moisture, large aggregates as well as electric conductivity were key factors influencing metal distributions in these zones. Although YRE was not heavily polluted by heavy metals, it should be vigilant for metal accumulation in 20-30 cm layer of oil spilled soils, and zones P and T with high RI greatly contributed by Cd.