Guillermo Zurita - Academia.edu (original) (raw)
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Papers by Guillermo Zurita
Chemosphere, 2007
Sodium monofluoroacetate (compound 1080) is one of the most potent pesticides. It is also a metab... more Sodium monofluoroacetate (compound 1080) is one of the most potent pesticides. It is also a metabolite of many other fluorinated compounds, including anticancer agents, narcotic analgesics, pesticides or industrial chemicals. Other sources of water contamination are the atmospheric degradation of hydrofluorocarbons and hydrochlorofluorocarbons. However, there is little information available about the adverse effects of sodium fluoroacetate in aquatic organisms. Firstly, the bacterium Vibrio fischeri (decomposer), the alga Chlorella vulgaris (1st producer) and the cladoceran Daphnia magna (1st consumer) were used for the ecotoxicological evaluation of SMFA. The most sensitive models were C. vulgaris and D. magna, with a NOAEL of 0.1 and an EC 50 of 0.5 mM at 72 h, respectively. According to the results after the acute exposure and due to its high biodegradation rate and low bioaccumulation potential, sodium fluoroacetate is most unlikely to produce deleterious effects to aquatic organisms. Secondly, two fish cell lines were employed to investigate the effects and mechanisms of toxicity in tissues from 2nd consumers. The hepatoma fish cell line PLHC-1 was more sensitive to SMFA than the fibroblast-like fish cell line RTG-2, being the uptake of neutral red the most sensitive bioindicator. Lysosomal function, succinate dehydrogenase and acetylcholinesterase activities were inhibited, glucose-6-phosphate dehydrogenase activity was particularly stimulated, and metallothionein and ethoxyresorufin-O-deethylase levels were not modified. Intense hydropic degeneration, macrovesicular steatosis and death mainly by necrosis but also by apoptosis were observed. Moreover, sulphydryl groups and oxidative stress could be involved in PLHC-1 cell death induced by SMFA more than changes in calcium homeostasis.
Toxicology Letters, 2010
Abstracts / Toxicology Letters 196S (2010) S37-S351 arately for 24 h or 22 h respectively of post... more Abstracts / Toxicology Letters 196S (2010) S37-S351 arately for 24 h or 22 h respectively of post-incubation. Cell surface expression of CD86 (and CD54 for h-CLAT/Episkin) was measured by flow cytometry and Episkin viability by MTT assay. After the proof of concept of the co-culture tests previously presented, the aim of this study was to assess and optimize some key experimental parameters. L'Oréal confirmed the choice of incubation and post-incubation times with Isoeugenol kinetic study; Water, DMSO, acetone and vegetal oil (Sunflower, corn or olive oils) were determined as suitable solvents with a harmonized treatment volume of 20 L; 28 chemicals were tested showing good prediction performance. 21 chemicals were tested with the co-culture system and Shiseido confirmed the co-culture system has an almost same predictive performance as h-CLAT. Furthermore, the exposure volume of chemicals for this co-culture system was optimized. The development of co-culture assays is on going and further research is necessary to confirm the added value of co-culture systems. Novel biomarkers in dendritic cells contribute in understanding the skin sensitization process N. Lambrechts, J. Hooyberghs, H. Witters, R. Van Den Heuvel, I. Nelissen, G. Schoeters
Aquatic Toxicology, 2005
There is limited information available about the potential environmental effects of chloroquine (... more There is limited information available about the potential environmental effects of chloroquine (CQ), a widely used antimalarial agent and a promising inexpensive drug in the management of HIV disease. The acute effects of CQ were studied using four ecotoxicological model systems. The most sensitive bioindicator was the immobilization of the cladoceran Daphnia magna, with an EC 50 of 12 M CQ at 72 h and a non-observed adverse effect level of 2.5 M CQ, followed very closely by the decrease of the uptake of neutral red and the reduction of the lysosomal function in the fish cell line PLHC-1 derived from the topminnow Poeciliopsis lucida, probably due to the selective accumulation of the drug into the lysosomes. There was significant cellular stress as indicated by the increases on metallothionein and glucose-6P dehydrogenase levels after 24 h of exposure and succinate dehydrogenase activity mainly after 48 h. No changes were observed for ethoxyresorufin-O-deethylase (EROD) activity. The least sensitive model was the inhibition of bioluminescence in the bacterium Vibrio fischeri. An increase of more than five-fold in the toxicity from 24 to 72 h of exposure was observed for the inhibition of the growth in the alga Chlorella vulgaris and the content of total protein and MTS tetrazolium salt metabolization in PLHC-1 cells. At the morphological level, the most evident alterations in PLHC-1 cultures were hydropic degeneration from 25 M CQ after 24 h of exposure and the presence of many cells with pyknotic nuclei, condensed cytoplasm and apoptosis with concentrations higher than 50 M CQ after 48 h of exposure. In conclusion, CQ should be classified as harmful to aquatic organisms.
Toxicology in Vitro, 2005
Cyanobacterial toxins, especially microcystins (MC), are found in eutrophied waters through the w... more Cyanobacterial toxins, especially microcystins (MC), are found in eutrophied waters through the world. Acute poisonings of animals and humans has been reported following MC exposure. In the present study, two fish cell lines, PLHC-1 and RTG-2, were evaluated after exposure to the cyanobacterial toxins MC-LR and MC-RR. The effects of different concentrations of the toxins were investigated in both cell lines at morphological and biochemical levels (total protein content, lactate dehydrogenase leakage, lysosomal activity and succinate dehydrogenase activity). The results obtained showed a decrease in protein content and no relevant increase in cell disruption, except for MC-LR in PLHC-1 cells. Morphological changes produced by microcystins were cellular swelling, blebbling, rounding, reduction in the cell number and increase in the number and size of lysosomal bodies. In addition, steatosis was produced in hepatoma PLHC-1 cells, particularly with MC-RR. Furthermore, the fish PLHC-1 cell line was more sensitive than RTG-2 cells to the cyanobacterial toxins compared, being the stimulation of the lysosomal function and the induction of steatosis the most specific changes detected.
Water Research, 2007
Ecotoxicity Cytotoxicity Alternative methods Aquatic environment a b s t r a c t Propyl gallate i... more Ecotoxicity Cytotoxicity Alternative methods Aquatic environment a b s t r a c t Propyl gallate is an antioxidant widely used in foods, cosmetics and pharmaceuticals. The occurrence and fate of additives in the aquatic environment is an emerging issue in environmental chemistry. To date, there is little available information about the adverse effects of propyl gallate on aquatic organisms. Therefore, the toxic effects were investigated, using five model systems from four trophic levels. The most sensitive system was the hepatoma fish cell line PLHC-1 according to total protein content, with an EC 50 of 10 mM and a NOAEL of 1 mM at 72 h, followed by the immobilization of Daphnia magna, the inhibition of bioluminescence of Vibrio fischeri, the salmonid fish cell line RTG-2 and the inhibition of the growth of Chlorella vulgaris. Although protein content, neutral red uptake, methylthiazol metabolization and acetylcholinesterase activity were reduced in PLHC-1 cells, stimulations were observed for lysosomal function, succinate dehydrogenase, glucose-6-phosphate dehydrogenase and ethoxyresorufin-O-deethylase activities. No changes were observed in metallothionein levels. The main morphological observations
Aquatic Toxicology, 2007
Gemfibrozil is a lipid-regulating agent widely used in patients at risk of coronary disease. Phar... more Gemfibrozil is a lipid-regulating agent widely used in patients at risk of coronary disease. Pharmaceutical products, such as gemfibrozil, are found in municipal effluents and represent a major source of contamination. To date, there is little available information about the adverse effects of gemfibrozil in aquatic organisms. For this reason, the toxic effects were investigated using model systems from four trophic levels. The most sensitive system was the immobilization of Daphnia magna, with a non-observed adverse effect level of 30 M and a mean effective concentration of 120 M after 72 h, followed by the inhibition of bioluminescence of Vibrio fischeri, the hepatoma fish cell line PLHC-1 line and the inhibition of the growth of Chlorella vulgaris. Although protein content, neutral red uptake, methylthiazol metabolization and lysosomal function were reduced in PLHC-1 cells, stimulations were observed for lysosomal function, metallothionein levels and succinate dehydrogenase, glucose-6-phosphate dehydrogenase and acetylcholinesterase activities. No changes were observed in ethoxyresorufin-O-deethylase activity. The main morphological alterations were hydropic degeneration and loss of cells. Modulation studies on gemfibrozil toxicity were also carried out. General antioxidants and calcium chelators did not modify the toxicity of gemfibrozil, whereas a Fe(III) chelator, a membrane permeable sulphydryl-protecting compound and glutathione level modifying agents did change the toxicity. One of the possible mechanisms of gemfibrozil toxicity seems to be the binding to sulphydryl groups, including those of glutathione. According to the result, gemfibrozil should be classified as harmful to aquatic organisms. However, comparing the concentrations in water and the toxicity quantified in the assayed systems, gemfibrozil is not expected to represent acute risk to the aquatic biota.
Chemosphere, 2007
Sodium monofluoroacetate (compound 1080) is one of the most potent pesticides. It is also a metab... more Sodium monofluoroacetate (compound 1080) is one of the most potent pesticides. It is also a metabolite of many other fluorinated compounds, including anticancer agents, narcotic analgesics, pesticides or industrial chemicals. Other sources of water contamination are the atmospheric degradation of hydrofluorocarbons and hydrochlorofluorocarbons. However, there is little information available about the adverse effects of sodium fluoroacetate in aquatic organisms. Firstly, the bacterium Vibrio fischeri (decomposer), the alga Chlorella vulgaris (1st producer) and the cladoceran Daphnia magna (1st consumer) were used for the ecotoxicological evaluation of SMFA. The most sensitive models were C. vulgaris and D. magna, with a NOAEL of 0.1 and an EC 50 of 0.5 mM at 72 h, respectively. According to the results after the acute exposure and due to its high biodegradation rate and low bioaccumulation potential, sodium fluoroacetate is most unlikely to produce deleterious effects to aquatic organisms. Secondly, two fish cell lines were employed to investigate the effects and mechanisms of toxicity in tissues from 2nd consumers. The hepatoma fish cell line PLHC-1 was more sensitive to SMFA than the fibroblast-like fish cell line RTG-2, being the uptake of neutral red the most sensitive bioindicator. Lysosomal function, succinate dehydrogenase and acetylcholinesterase activities were inhibited, glucose-6-phosphate dehydrogenase activity was particularly stimulated, and metallothionein and ethoxyresorufin-O-deethylase levels were not modified. Intense hydropic degeneration, macrovesicular steatosis and death mainly by necrosis but also by apoptosis were observed. Moreover, sulphydryl groups and oxidative stress could be involved in PLHC-1 cell death induced by SMFA more than changes in calcium homeostasis.
Toxicology Letters, 2010
Abstracts / Toxicology Letters 196S (2010) S37-S351 arately for 24 h or 22 h respectively of post... more Abstracts / Toxicology Letters 196S (2010) S37-S351 arately for 24 h or 22 h respectively of post-incubation. Cell surface expression of CD86 (and CD54 for h-CLAT/Episkin) was measured by flow cytometry and Episkin viability by MTT assay. After the proof of concept of the co-culture tests previously presented, the aim of this study was to assess and optimize some key experimental parameters. L'Oréal confirmed the choice of incubation and post-incubation times with Isoeugenol kinetic study; Water, DMSO, acetone and vegetal oil (Sunflower, corn or olive oils) were determined as suitable solvents with a harmonized treatment volume of 20 L; 28 chemicals were tested showing good prediction performance. 21 chemicals were tested with the co-culture system and Shiseido confirmed the co-culture system has an almost same predictive performance as h-CLAT. Furthermore, the exposure volume of chemicals for this co-culture system was optimized. The development of co-culture assays is on going and further research is necessary to confirm the added value of co-culture systems. Novel biomarkers in dendritic cells contribute in understanding the skin sensitization process N. Lambrechts, J. Hooyberghs, H. Witters, R. Van Den Heuvel, I. Nelissen, G. Schoeters
Aquatic Toxicology, 2005
There is limited information available about the potential environmental effects of chloroquine (... more There is limited information available about the potential environmental effects of chloroquine (CQ), a widely used antimalarial agent and a promising inexpensive drug in the management of HIV disease. The acute effects of CQ were studied using four ecotoxicological model systems. The most sensitive bioindicator was the immobilization of the cladoceran Daphnia magna, with an EC 50 of 12 M CQ at 72 h and a non-observed adverse effect level of 2.5 M CQ, followed very closely by the decrease of the uptake of neutral red and the reduction of the lysosomal function in the fish cell line PLHC-1 derived from the topminnow Poeciliopsis lucida, probably due to the selective accumulation of the drug into the lysosomes. There was significant cellular stress as indicated by the increases on metallothionein and glucose-6P dehydrogenase levels after 24 h of exposure and succinate dehydrogenase activity mainly after 48 h. No changes were observed for ethoxyresorufin-O-deethylase (EROD) activity. The least sensitive model was the inhibition of bioluminescence in the bacterium Vibrio fischeri. An increase of more than five-fold in the toxicity from 24 to 72 h of exposure was observed for the inhibition of the growth in the alga Chlorella vulgaris and the content of total protein and MTS tetrazolium salt metabolization in PLHC-1 cells. At the morphological level, the most evident alterations in PLHC-1 cultures were hydropic degeneration from 25 M CQ after 24 h of exposure and the presence of many cells with pyknotic nuclei, condensed cytoplasm and apoptosis with concentrations higher than 50 M CQ after 48 h of exposure. In conclusion, CQ should be classified as harmful to aquatic organisms.
Toxicology in Vitro, 2005
Cyanobacterial toxins, especially microcystins (MC), are found in eutrophied waters through the w... more Cyanobacterial toxins, especially microcystins (MC), are found in eutrophied waters through the world. Acute poisonings of animals and humans has been reported following MC exposure. In the present study, two fish cell lines, PLHC-1 and RTG-2, were evaluated after exposure to the cyanobacterial toxins MC-LR and MC-RR. The effects of different concentrations of the toxins were investigated in both cell lines at morphological and biochemical levels (total protein content, lactate dehydrogenase leakage, lysosomal activity and succinate dehydrogenase activity). The results obtained showed a decrease in protein content and no relevant increase in cell disruption, except for MC-LR in PLHC-1 cells. Morphological changes produced by microcystins were cellular swelling, blebbling, rounding, reduction in the cell number and increase in the number and size of lysosomal bodies. In addition, steatosis was produced in hepatoma PLHC-1 cells, particularly with MC-RR. Furthermore, the fish PLHC-1 cell line was more sensitive than RTG-2 cells to the cyanobacterial toxins compared, being the stimulation of the lysosomal function and the induction of steatosis the most specific changes detected.
Water Research, 2007
Ecotoxicity Cytotoxicity Alternative methods Aquatic environment a b s t r a c t Propyl gallate i... more Ecotoxicity Cytotoxicity Alternative methods Aquatic environment a b s t r a c t Propyl gallate is an antioxidant widely used in foods, cosmetics and pharmaceuticals. The occurrence and fate of additives in the aquatic environment is an emerging issue in environmental chemistry. To date, there is little available information about the adverse effects of propyl gallate on aquatic organisms. Therefore, the toxic effects were investigated, using five model systems from four trophic levels. The most sensitive system was the hepatoma fish cell line PLHC-1 according to total protein content, with an EC 50 of 10 mM and a NOAEL of 1 mM at 72 h, followed by the immobilization of Daphnia magna, the inhibition of bioluminescence of Vibrio fischeri, the salmonid fish cell line RTG-2 and the inhibition of the growth of Chlorella vulgaris. Although protein content, neutral red uptake, methylthiazol metabolization and acetylcholinesterase activity were reduced in PLHC-1 cells, stimulations were observed for lysosomal function, succinate dehydrogenase, glucose-6-phosphate dehydrogenase and ethoxyresorufin-O-deethylase activities. No changes were observed in metallothionein levels. The main morphological observations
Aquatic Toxicology, 2007
Gemfibrozil is a lipid-regulating agent widely used in patients at risk of coronary disease. Phar... more Gemfibrozil is a lipid-regulating agent widely used in patients at risk of coronary disease. Pharmaceutical products, such as gemfibrozil, are found in municipal effluents and represent a major source of contamination. To date, there is little available information about the adverse effects of gemfibrozil in aquatic organisms. For this reason, the toxic effects were investigated using model systems from four trophic levels. The most sensitive system was the immobilization of Daphnia magna, with a non-observed adverse effect level of 30 M and a mean effective concentration of 120 M after 72 h, followed by the inhibition of bioluminescence of Vibrio fischeri, the hepatoma fish cell line PLHC-1 line and the inhibition of the growth of Chlorella vulgaris. Although protein content, neutral red uptake, methylthiazol metabolization and lysosomal function were reduced in PLHC-1 cells, stimulations were observed for lysosomal function, metallothionein levels and succinate dehydrogenase, glucose-6-phosphate dehydrogenase and acetylcholinesterase activities. No changes were observed in ethoxyresorufin-O-deethylase activity. The main morphological alterations were hydropic degeneration and loss of cells. Modulation studies on gemfibrozil toxicity were also carried out. General antioxidants and calcium chelators did not modify the toxicity of gemfibrozil, whereas a Fe(III) chelator, a membrane permeable sulphydryl-protecting compound and glutathione level modifying agents did change the toxicity. One of the possible mechanisms of gemfibrozil toxicity seems to be the binding to sulphydryl groups, including those of glutathione. According to the result, gemfibrozil should be classified as harmful to aquatic organisms. However, comparing the concentrations in water and the toxicity quantified in the assayed systems, gemfibrozil is not expected to represent acute risk to the aquatic biota.