Antimicrobial activity of polyoxometalate ionic liquids (POM-ILs) against clinically relevant pathogens

Antimicrobial activity of polyoxometalate ionic liquids (POM-ILs) against clinically relevant pathogens

P-05-04 / Toxicology Letters 280S (2017) S191–S194 vitro and in vivo experimental models. Chemoprevention is a novel aspect referring to the use of n...

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P-05-04 / Toxicology Letters 280S (2017) S191–S194

vitro and in vivo experimental models. Chemoprevention is a novel aspect referring to the use of natural, semisynthetic or synthetic compounds to halt or reverse tumor formation and progression. Chemopreventive agents are classified into natural compounds or phytochemicals such as silymarin, quercetin, and curcumin, or synthetic chemicals; namely, retinoic acid and melatonin. Aims: Firstly, identification of the critical genes in noncancerous kidney RPTEC/TERT1 cells which were dysregulated by KBrO3 -induced DNA mutation. The status of the dysregulated genes, whether up- or down-regulated following KBrO3 exposure, was compared with their status in cancerous renal cells. These genes regulate inflammation, apoptosis, angiogenesis, and EMT. Secondly, identification of a chemopreventive agent that is capable of blocking the oxidative burden and DNA adduct formation induced by KBrO3 , as well as suppressing dysregulation of critical genes affected by KBrO3 was achieved. Conclusion: Our study confirmed that natural chemopreventives or phytochemicals were more effective to protect kidney cells against the carcinogenic potential of KBrO3 than the synthetic chemopreventives. http://dx.doi.org/10.1016/j.toxlet.2017.07.542 P-05-04-07 Polycyclic aromatic hydrocarbons show androgenic and antiandrogenic activity in yeast expressing human androgen receptor ˛ Sylwia Stypuła-Trebas, Maria Minta, Lidia Radko, Andrzej Posyniak Department of Pharmacology and Toxicology, National Veterinary Research Institute, Puławy, Poland Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants, suspected carcinogens and potential endocrine disrupters. They are known to mediate their estrogenic and antiestrogenic activity through the aryl hydrocarbon and estrogen receptors. Much less is known about their effect on male reproductive system and androgen receptor signalling. Thus, we have characterized 7 PAHs commonly found in the environment: benz[a]anthracene (BaA), benzo[a]pyrene (BaP), benzo[k]fluoranthene (BkF), benzo[b]fluoranthene (BbF), benzo[a]fluorenone (BaF), antraquinone (Ant) and chrysene (Chr) for their androgenic and antiandrogenic activity in yeast-based recombinant transactivation assay. The compounds were dosed at 9 concentrations ranging from 10 nM to 300 mM alone or in binary mixtures with testosterone (17bT, 50 nM). Each bioassay was performed at least two times. The cytotoxicity, EC50, relative transactivation activity (RTA) and relative agonistic activities (RAA) were calculated. Our results show that all PAHs except Chr are partial androgen agonists with RTA from 4.7 to 20.6%, and RAA from 0.002 to 0.009. Apart from androgenic activity, 5 PAHs inhibited the response of 50 nM 17bT. The rank of antiandrogenic activity is as follows: BAA > BaF > Ant > BaP > BkF. Maximal and minimal inhibitory effects were 60% (BaA, BaF) and 18% (BkF) respectively. Taken together, it seems possible that PAHs exert adverse effects on male reproductive systems of human and animals through disruption of androgen receptor signalling. It is therefore important to clarify the relevance of observed effects for in vivo situation. http://dx.doi.org/10.1016/j.toxlet.2017.07.543

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P-05-04-08 Antimicrobial activity of polyoxometalate ionic liquids (POM-ILs) against clinically relevant pathogens Anna-Liisa Kubo 1 , Lea Kremer 2 , Sven Herrmann 2 , Scott G. Mitchell 3 , Olesja M. Bondarenko 1 , Anne Kahru 1,4 , Carsten Streb 2 1

Laboratory of Environmental Toxicology, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia 2 Institute of Inorganic Chemistry, Ulm University, Ulm, Germany 3 Instituto de Ciencia de Materiales de Aragon, CISC, Universidad de Zaragoza, Zaragoza, Spain 4 Estonian Academy of Sciences, Tallinn, Estonia Spreading microbial infections are currently a major public health concern, thus novel approaches are required to combat multiresistant bacterial infections. Here we present a systematic investigation of a new class of antimicrobials, namely polyoxometalate ionic liquids (POM-ILs). The POM-ILs involved feature Keggin-type anions [␣-SiW11 O39 ]8− and tetraalkyl ammonium cations. Here we report the minimum bactericidal concentrations (MBC), minimum inhibitory concentrations (MIC) and growth inhibition properties (EC50) in Mueller Hinton broth of POM-ILs based on the tetraalkyl ammonium cations Q6 (= N(C6 H13 )4 + ), Q7 (= N(C7 H15 )4 + ) and Q8 (= N(C8 H17 )4 + ) with lacunary Keggin anions [a-SiW11 O39 ]8− . Our study showed that (i) all synthesised POM-ILs were causing susceptibility of medically relevant Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa and especially of Grampositive Staphylococcus aureus and that (ii) antimicrobial properties can be improved by modification of the cation alkyl chain length: the longer-chain POM-ILs Q7 -IL and particularly Q8 -IL showed remarkably better efficiency when compared with Q6 -IL. Interestingly, the Gram-positive bacteria S. aureus were especially sensitive to all types of tested POM-ILs and MIC values as low as 2–10 mg/L were observed. Due to the unique materials properties of the POMILs, such as high viscosity and water immiscibility, they have a wide area of possible applications from surface coatings to water decontamination. The work of Anna-Liisa Kubo was supported by ERC Grant IUT 23-5. http://dx.doi.org/10.1016/j.toxlet.2017.07.544 P-05-04-09 Downregulation of long noncoding RNA UCA1 is involved in Het-1A cells malignant transformation induced by N-nitrosamines combined microcystin-LR Xianghu Wang, Feifei Qiu, Zhikui Gao, Muhe Shang, Mengxin Liu, Lihong Yin, Yuepu Pu, Ran Liu School of Public Health, Southeast University, Nanjing, China It has been reported the toxic metabolite microcystins may contribute to the aggravation of carcinoma induced by Nnitrosamines, a class of known carcinogens. Previously, our study indicates that microcystin-LR (MC-LR) acts as promoter of N-nitrosomethylbenzylamine (NMBzA) induced esophageal carcinogenesis. However, the underlying mechanism is still unknown. Recently, long noncoding RNAs in toxicology have attracted great attention. We previously showed that long noncoding RNA UCA1 is downregulated in esophageal cancer (EC). Here, we evaluated the roles of UCA1 in NMBzA combined MC-LR induced malignant transformation of human esophageal epithelial (Het-1A) cells. Results of the colony formation in soft agar indicate that