Xinghao Wang,Ruijuan Qu,Zhongbo Wei,Xi Yang,Zunyao Wang
Mercury (Hg) compounds are widely distributed toxic environmental and industrial pollutants and they may bring danger to growth and development of aquatic organisms. The distribution of Hg species in the 3 percent NaCl solution was calculated using the chemical equilibrium model Visual MINTEQ, which demonstrated that Hg was mainly complexed by chlorides in the pH range 5.0–9.0 and the proportions of HgCl 4 2− , HgCl 3 − and HgCl 2 (aq) reached to 95 percent of total Hg. Then the effects of cations (Ca 2+ , Mg 2+ , K + and H + ), anions (HCO 3 − , NO 3 − , SO 4 2− and HPO 4 2− ) and complexing agents (ethylene diamine tetraacetic acid (EDTA) and dissolved organic matter (DOM)) on Hg toxicity to Photobacterium phosphoreum were evaluated in standardized 15 min acute toxicity tests . The significant increase of 6.3-fold in EC 50 data with increasing pH was observed over the tested pH range of 5.0–8.0, which suggested the possible competition between hydroxyl and the negatively charged chloro-complex. By contrast, it was found that major cations (Ca 2+ , Mg 2+ and K + ) have little effect on Hg toxicity to P. phosphoreum . An interesting finding was that the addition of HPO 4 2− significantly increased Hg toxicity, which may imply that the addition of phosphate increased the soluble Hg–chloro complex species. Additions of complexing agents (EDTA and DOM) into the exposure water increased Hg bioavailability via complexation of Hg. Finally, a model which incorporated the effect of pH, HPO 4 2− , HCO 3 − , SO 4 2− and DOM on Hg toxicity was developed to predict acute Hg toxicity for P. phosphoreum , which may be a useful tool in setting realistic water quality criteria for different types of water.
Wang Xue,Han Lifeng,Li Gentao,Peng Wei,Gao Xiumei,Klaassen Curtis D,Fan Guanwei,Zhang Youcai
Mercury accumulates in kidneys and produces acute kidney injury. Semen cassiae (SC), a widely consumed tea and herbal medicine in Eastern Asia, has been reported to have protective effects on kidneys. In this study, SC extract was shown to almost abolish the histological alterations induced by mercuric chloride in rat kidneys. A total of 22 compounds were isolated from SC, and 1,7,8-methoxyl-2-hydroxyl-3-methyl-anthraquinone was detected in SC for the first time. Among the eight compounds identified in the blood of rats after SC treatment, six were strong inhibitors of human organic anion transporter 1 and 3 (OAT1 and OAT3). Inhibitory studies revealed that OAT1 and OAT3 were inhibited by SC constituents, in both a competitive and noncompetitive manner. Both OAT1- and OAT3-overexpressing cells were susceptible to the cytotoxicity of the cysteine–mercury conjugate, but only OAT1-overexpressing cells could be protected by 200 μM probenecid or 10 μM of the eight inhibitors in SC, suggesting that OAT1 is the major determinant in the cellular uptake of mercury. To facilitate the identification of inhibitors of OAT1 and OAT3, models of OAT1 and OAT3 were constructed using recently determined protein templates. By combining in silico and in vitro methods, inhibitors of OAT1 and OAT3 were predicted and validated from SC constituents. Collectively, the present study suggests that additional inhibitors of OAT1 and OAT3 can be predicted and validated from natural products by combining docking and in vitro screening, and could be a source of pharmaceutical compounds for developing treatments for mercury-induced kidney injury.
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