The fungicide difenoconazole has been frequently detected in agricultural products, soils and surface waters, causing increasingly public concern due to toxicological properties. Although systemic triazole fungicides can inhibit the enzymatic activity of many CYP450 isozymes, how difenoconazole affects the human CYP3A4 still remains largely unknown. We thus investigated the effect of difenoconazole on normal mRNA expression and protein expression of human CYP3A4 by real-time quantitative PCR and western blot, respectively. Results show that the exposure to difenoconazole from 0.01 to 0.5 μM for 24 h down-regulates mRNA expression levels of human CYP3A4 in HepG2 cells. We also found that difenoconazole could inhibit the enzymatic activity of human CYP3A4 in a concentration-dependent mode. The IC50 of difenoconazole for inhibition of CYP3A4 activity is 0.41 µM, showing a stronger inhibitor in comparison with ketoconazole. Overall, our findings indicate the potential risk of difenoconazole for the disruption of human CYP3A4. 相似文献
Halogenated biphenyls are worldwide persistent pollutants of great environmental concern. In particular, polychlorinated biphenyls and polybrominated biphenyls have been globally used for industrial purposes until they were found highly toxic, mutagenic and carcinogenic to humans. Therefore, ecological strategies to remove halogenated biphenyls, such as enzyme-catalyzed degradation, are needed. Here, we studied the effect of substitution of F, Cl, Br or I at the 4,4′-positions of 2,3-dihydro-2,3-dihydroxybiphenyl-2,3-dehydrogenase (BphB) on the degradation of halogenated biphenyls by quantum and molecular mechanics. Results show that Boltzmann-weighted average degradation barriers of substituted BphB are all lower than the unsubstituted biphenyl, except for chlorinated biphenyl. The roles of residues nearby the active site, e.g., isoleucine89, asparagine115, serine142, asparagine143, proline184, methionine187 and threonine189, were also investigated.
Taihu Lake is the third largest freshwater lake in China. In recent years, the water pollution of cyanobacteria blooms has become a severe problem in this area. Microcystins (MCs) are an important group of toxic compounds mainly produced by some cyanobacteria species and have both acute and chronic hepatotoxic effects on animals and humans. This paper presents the first data on the identification and detection of MCs in both natural occurring cyanobacteria blooms and surface water samples (0-0.5 m), collected from Meiliang Bay, Taihu Lake, China. A conventional method for extraction and isolation of MCs from cyanobacteria blooms was applied. High-performance liquid chromatography (HPLC) analysis showed that the main toxic component in the cyanobacteria materials was MC-LR. The monoclonal antibody (mAb) against MC-LR produced by hybridoma technique was employed for direct competitive ELISA to detect the concentrations of MCs in bloom and water samples collected in 2001. The results not only revealed the presence of MCs but also temporal variations of MCs levels of three sampling stations in Meiliang Bay in 1 year. It is obvious that the MC contents were relatively higher during warm months and related with the status of eutrophication. Our study indicates the threat associated with MCs in water body of Taihu Lake. To prevent the MCs potential hazard on public health in this area, some necessary measures of monitoring and control of growth of cyanobacteria are urgently needed. 相似文献