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Evaluation of the genotoxic effects of indapamide in human lymphocytes in vitro by sister chromatid exchange test
Abstracts / Toxicology Letters 258S (2016) S62–S324
P11-005 Evaluation of the genotoxic effects of indapamide in human lymphocytes in vitro by sister chromatid exchange test E. Avuloglu Yilmaz ∗ , F. Ünal, D. Yüzbas¸ıo˘glu Department of Biology, Gazi University, Ankara, Turkey Indapamide is a thiazide-like diuretic drug active ingredient used in the treatment of hypertension. The large majority of hypertensive patients need long-term administration of this drug. However, no data are available on genotoxicity of indapamide in human peripheral lymphocytes. The purpose of this study was to evaluate the potential genotoxic effect of indapamide by using in vitro sister chromatid exchange (SCE) test. Mitotic (MI) and replication (RI) indices were also calculated. For this purpose, peripheral blood obtained from three healthy young donors, a man and two women, was treated with four different concentrations (18.75, 37.50, 75.00, and 100.00 g/mL) of indapamide in culture conditions for 24 and 48 h. A negative, a solvent (%75 methanol) and a positive control (mitomycin-C) were also used for each treatment. Results of this experiment showed that indapamide did not affect SCE frequency compared to negative and solvent control at all the concentrations for 24 h treatment. On the other hand, indapamide significantly increased the SCE/cell ratio at two highest concentrations at 48 h period compared to negative and solvent controls. In addition, this chemical decreased the MI in all the concentrations compared with the negative and solvent controls both at 24 h and 48 h periods (except 18.75 g/mL, 48 h). However, indapamide did not affect replication index. The results obtained in this study suggest that other tests should be performed to clarify whether this active ingredient has genotoxicity in human lymphocytes.
S205
Sixty-three children aged 6–12 years were enrolled in this study: 43 from a rural area and 20 from an urban area. Metal blood levels were quantified by inductively coupled plasma mass spectrometry (ICP-MS). Determinations of microalbuminuria (mALB) level and N-acetyl-beta-d-glucosaminidase (NAG) activity were performed. The NEUPSILIN-INF battery was used to assess the following cognitive functions: attention, perception, memory, language, arithmetic skills, and executive functions. Mn and Hg blood levels were significantly higher (p < 0.001) in rural children than urban ones, respectively 26.9 ± 0.77 and 6.1 ± 0.9 g L−1 for rural, and 19.25 ± 0.97 and 1.1 ± 0.07 g L−1 for urban children. NAG activity was significantly higher in rural (5.2 ± 0.4 U g−1 creatinine) than urban children (3.4 ± 0.3 U g−1 creatinine) (p < 0.05). Additionally, mALB levels were significantly increased in rural (11.3 ± 1.5 mg g−1 creatinine) when compared to urban children (7.02 ± 1.4 mg g−1 creatinine) (p < 0.05). Significant negative correlations were found between Mn and memory and perception (p < 0.05); as well as Hg and memory, perception, arithmetic skills, and language (p < 0.05). Significant positive correlation was observed between Hg and NAG activity (p < 0.05). These data suggested that children environmentally exposed to Mn and Hg may present kidney dysfunction and cognitive impairments. http://dx.doi.org/10.1016/j.toxlet.2016.06.1747
P12-002 Nonlinear responses to Cadmium toxicity in zebrafish E. Renieri 1,∗ , A. Alegakis 1 , E. Vakonaki 1 , D. Sfakianakis 2 , M. Goumenou 3 , I. Safenkova 4 , E. Slutskaya 4 , M. Kentouri 2 , P. Divanach 5 , B. Dzantiev 4 , A. Tsatsakis 1
http://dx.doi.org/10.1016/j.toxlet.2016.06.1746 1
P12 – Human and environmental risk assessment P12-001 Blood levels of manganese and mercury and effects on kidney and cognitive function in children environmentally exposed from Southern Brazil S.N. Nascimento 1,∗ , G. Göethel 1 , A. Barth 1 , M. Baierle 1 , A.M. Moro 1 , N. Brucker 1 , M.F. Charão 1 , E. Sauer 1 , B. Gauer 1 , J. Fumagalli 2 , R. Moresco 3 , T. Saint’ Pierre 4 , A. Gioda 4 , S.C. Garcia 1 1
Laboratory of Toxicology (LATOX), Department of Analyses, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil 2 Institute of Psychology, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil 3 Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analyses, Federal University of Santa Maria (UFSM), Santa Maria, RS, Brazil 4 Department of Chemistry, Pontifical Catholic University of Rio de Janeiro (PUC-Rio), Rio de Janeiro, RJ, Brazil Children are a risk group especially sensitive to metals exposure. The aim of this study was to evaluate the blood concentrations of Mn and Hg in children from rural and urban areas, and to investigate the associations between metals and adverse effects on kidney and cognitive functions.
Laboratory of Toxicology, University of Crete, Medical School, Crete, Greece 2 Biology Department, University of Crete, Heraklio, Crete, Greece 3 European Food Safety Authority, Parma, Italy 4 A.N. Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russia 5 Institute of Marine Biology, Biotechnology and Aquaculture, Hellenic Center for Marine Research, Iraklion, Crete, Greece Cadmium toxicity in aquatic organisms is rising to a major topic, being closely linked to human exposure primarily through diet. The aim of the present study was to investigate the Cd burden in zebrafish (DR) exposed to concentrations ranging from environmental to toxic and its association with fish mortality. For this purpose 10 zebrafish for each dose level were placed in 36 L water tanks and they were exposed for 30 days at 0.0, 5.0, 25, 50, 75, 100 and 1000 g of waterborne Cd per liter. Tissue samples were collected at death or end of the experiment and Cd burden was determinated by an in house ICP-MS method and was found to range from 3.1 to 29.1 ng/mg. Cd exposure levels were significantly correlated with the log Cd level in fish tissues (r = 0.535, p < 0.001). Median OS (in days) was estimated for consolidated Cd concentrations (25–50 g/L and 75–100 g/L) showing mortality greater than 50%. The median OS for 25–50 g/L and 75–100 g/L was 11.0 (5.3–16.7) and 8.0 (7.1–8.9) respectively. Surprisingly, fishes exposed to the highest Cd concentration of 1000 g/L and having the highest Cd burden in their tissues (mean = 12.2 ng/mg), survived longer exerting a mean OS equal to 29.2 (95% CI: 27.8–30.7). A probable hypothesis could be that at high exposure levels a defensive mechanism against Cd toxicity is triggered, probably due to modulation of detoxification mechanisms, resulting in altered Cd sensitivity.
P11-005 Evaluation of the genotoxic effects of indapamide in human lymphocytes in vitro by sister chromatid exchange test E. Avuloglu Yilmaz ∗ , F. Ünal, D. Yüzbas¸ıo˘glu Department of Biology, Gazi University, Ankara, Turkey Indapamide is a thiazide-like diuretic drug active ingredient used in the treatment of hypertension. The large majority of hypertensive patients need long-term administration of this drug. However, no data are available on genotoxicity of indapamide in human peripheral lymphocytes. The purpose of this study was to evaluate the potential genotoxic effect of indapamide by using in vitro sister chromatid exchange (SCE) test. Mitotic (MI) and replication (RI) indices were also calculated. For this purpose, peripheral blood obtained from three healthy young donors, a man and two women, was treated with four different concentrations (18.75, 37.50, 75.00, and 100.00 g/mL) of indapamide in culture conditions for 24 and 48 h. A negative, a solvent (%75 methanol) and a positive control (mitomycin-C) were also used for each treatment. Results of this experiment showed that indapamide did not affect SCE frequency compared to negative and solvent control at all the concentrations for 24 h treatment. On the other hand, indapamide significantly increased the SCE/cell ratio at two highest concentrations at 48 h period compared to negative and solvent controls. In addition, this chemical decreased the MI in all the concentrations compared with the negative and solvent controls both at 24 h and 48 h periods (except 18.75 g/mL, 48 h). However, indapamide did not affect replication index. The results obtained in this study suggest that other tests should be performed to clarify whether this active ingredient has genotoxicity in human lymphocytes.
S205
Sixty-three children aged 6–12 years were enrolled in this study: 43 from a rural area and 20 from an urban area. Metal blood levels were quantified by inductively coupled plasma mass spectrometry (ICP-MS). Determinations of microalbuminuria (mALB) level and N-acetyl-beta-d-glucosaminidase (NAG) activity were performed. The NEUPSILIN-INF battery was used to assess the following cognitive functions: attention, perception, memory, language, arithmetic skills, and executive functions. Mn and Hg blood levels were significantly higher (p < 0.001) in rural children than urban ones, respectively 26.9 ± 0.77 and 6.1 ± 0.9 g L−1 for rural, and 19.25 ± 0.97 and 1.1 ± 0.07 g L−1 for urban children. NAG activity was significantly higher in rural (5.2 ± 0.4 U g−1 creatinine) than urban children (3.4 ± 0.3 U g−1 creatinine) (p < 0.05). Additionally, mALB levels were significantly increased in rural (11.3 ± 1.5 mg g−1 creatinine) when compared to urban children (7.02 ± 1.4 mg g−1 creatinine) (p < 0.05). Significant negative correlations were found between Mn and memory and perception (p < 0.05); as well as Hg and memory, perception, arithmetic skills, and language (p < 0.05). Significant positive correlation was observed between Hg and NAG activity (p < 0.05). These data suggested that children environmentally exposed to Mn and Hg may present kidney dysfunction and cognitive impairments. http://dx.doi.org/10.1016/j.toxlet.2016.06.1747
P12-002 Nonlinear responses to Cadmium toxicity in zebrafish E. Renieri 1,∗ , A. Alegakis 1 , E. Vakonaki 1 , D. Sfakianakis 2 , M. Goumenou 3 , I. Safenkova 4 , E. Slutskaya 4 , M. Kentouri 2 , P. Divanach 5 , B. Dzantiev 4 , A. Tsatsakis 1
http://dx.doi.org/10.1016/j.toxlet.2016.06.1746 1
P12 – Human and environmental risk assessment P12-001 Blood levels of manganese and mercury and effects on kidney and cognitive function in children environmentally exposed from Southern Brazil S.N. Nascimento 1,∗ , G. Göethel 1 , A. Barth 1 , M. Baierle 1 , A.M. Moro 1 , N. Brucker 1 , M.F. Charão 1 , E. Sauer 1 , B. Gauer 1 , J. Fumagalli 2 , R. Moresco 3 , T. Saint’ Pierre 4 , A. Gioda 4 , S.C. Garcia 1 1
Laboratory of Toxicology (LATOX), Department of Analyses, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil 2 Institute of Psychology, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil 3 Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analyses, Federal University of Santa Maria (UFSM), Santa Maria, RS, Brazil 4 Department of Chemistry, Pontifical Catholic University of Rio de Janeiro (PUC-Rio), Rio de Janeiro, RJ, Brazil Children are a risk group especially sensitive to metals exposure. The aim of this study was to evaluate the blood concentrations of Mn and Hg in children from rural and urban areas, and to investigate the associations between metals and adverse effects on kidney and cognitive functions.
Laboratory of Toxicology, University of Crete, Medical School, Crete, Greece 2 Biology Department, University of Crete, Heraklio, Crete, Greece 3 European Food Safety Authority, Parma, Italy 4 A.N. Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russia 5 Institute of Marine Biology, Biotechnology and Aquaculture, Hellenic Center for Marine Research, Iraklion, Crete, Greece Cadmium toxicity in aquatic organisms is rising to a major topic, being closely linked to human exposure primarily through diet. The aim of the present study was to investigate the Cd burden in zebrafish (DR) exposed to concentrations ranging from environmental to toxic and its association with fish mortality. For this purpose 10 zebrafish for each dose level were placed in 36 L water tanks and they were exposed for 30 days at 0.0, 5.0, 25, 50, 75, 100 and 1000 g of waterborne Cd per liter. Tissue samples were collected at death or end of the experiment and Cd burden was determinated by an in house ICP-MS method and was found to range from 3.1 to 29.1 ng/mg. Cd exposure levels were significantly correlated with the log Cd level in fish tissues (r = 0.535, p < 0.001). Median OS (in days) was estimated for consolidated Cd concentrations (25–50 g/L and 75–100 g/L) showing mortality greater than 50%. The median OS for 25–50 g/L and 75–100 g/L was 11.0 (5.3–16.7) and 8.0 (7.1–8.9) respectively. Surprisingly, fishes exposed to the highest Cd concentration of 1000 g/L and having the highest Cd burden in their tissues (mean = 12.2 ng/mg), survived longer exerting a mean OS equal to 29.2 (95% CI: 27.8–30.7). A probable hypothesis could be that at high exposure levels a defensive mechanism against Cd toxicity is triggered, probably due to modulation of detoxification mechanisms, resulting in altered Cd sensitivity.