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Possible approaches to the development of universal cholinesterase reactivator
Abstracts / Toxicology Letters 205S (2011) S60–S179
0.10–0.267; Zn 7.11–21.88 g/g wet weight, respectively. Levels of Cd, Hg, Pb, Ni were not exceeding the corresponding provisional tolerable weekly intake (PTWI) values. For average consumers, target hazard quotient (THQ) values of inorganic As, Cd, Hg, Pb and Ni indicated the absence of health risks through consumption of the fish species analyzed. Cancer risk estimate for inorganic As (5.7 × 10−6 ) from consuming these fish species was lower than 10−5 (acceptable risk). Our results suggest that there is a need for more information on total dietary exposure of inorganic As and supports the importance of speciation analysis for arsenic in seafood for more appropriate risk assessment of inorganic As in fish species. doi:10.1016/j.toxlet.2011.05.426
P1193 Single and combined effects associated with two xenobiotics widely used in intensive aquaculture on European sea bass (Dicentrarchus labrax) M.A. Jerbi 1,∗ , Z. Ouanes 2 , R. besbes 3 , Z. Haouas 4 , L. Achour 1 , A. Kacem 1 1
Unité De Recherche Génome, Diagnostic Immunitaire Et Valorisation, ISBM, Monastir, Tunisia, 2 Marine and Environmental Toxicology, UR 09-03-IPEIS, Sfax University, Sfax, Tunisia, 3 Institut National des Sciences et Technologies de la Mer, Monastir, Tunisia, 4 Laboratoire d’Histologie et de Cytogénétique, Faculté de Médecine de Monastir, Monastir, Tunisia Several chemicals are used in aquaculture to prevent or to treat diseases outbreaks. These substances are mainly administered by two different modes; by prolonged bath or by complexation with the diet. In the case of intensive aquaculture, the most applied by bath chemicals are formaldehyde (FA) 37% and oxytetracycline (OTC). Under therapeutic use, FA 37% is applied prophylactically at 200 ml/m3 , whereas OTC is used curatively at 40 g/m3 . The goal of the present study is to assess adverse effects associated with the European sea bass (D. labrax) exposure to FA37% and OTC under the same conditions being applied in intensive aquaculture systems. To this end the micronuclei (MN) assay was applied in erythrocytic cells to assess their genotoxicity and cytotoxicity. In parallel a histopathological survey and a study of the oxidative status of the liver were also achieved. Our results showed that both tested chemicals presented genotoxic and cytotoxic potential following a time-dependent pattern. Histologically viewing, it was obvious that both FA and OTC have induced sinusoid dilatation and blood congestion. Intensive vacuolisation and focal necrosis were also observed. These results are confirmed by the biochemical analysis where catalase activity and malondialdehyde have shown a significant increase in reference to control (p ≤ 0.05). Captivatingly, the combined treatment induces a cumulative effect particularly well pronounced after 15 days of exposure suggesting the critical hazards associated to FA and OTC when applied or released together. doi:10.1016/j.toxlet.2011.05.427
S119
P1194 Possible approaches to the development of universal cholinesterase reactivator J. Bajgar 1,∗ , J. Kassa 1 , M. Pohanka 2 1
Toxicology, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic, 2 Center of Advanced Studies, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic Based on our knowledge of the mechanism of nerve agents/organophosphates (OP), anticholinergics, cholinesterase reactivators (oximes) and anticonvulsants are used. At present, there is not an universal reactivator able to reactivate AChE inhibited by all nerve agents/OP. Some steps of development of this antidote are described. Literature survey and other information are necessary; after this stage, inhibition/reactivation potency of the nerve agent/reactivator to AChE can be used to characterize the toxic/therapeutic effects (inhibition/reactivation of cholinesterases) followed by determination of the reactivator’s effect in vitro including molecular modelling. As the first information in vivo is simple characterization by toxicity and later on, reactivation potency in vivo and therapeutic efficacy following administration of various antidotes or their combinations is provided. For further studies in vivo, AChE inhibition/reactivation in different tissues are determined. Quantitative histochemical determination of AChE activity allows fine differentiation among various brain structures. Blood levels of nerve agents and antidotes are necessary part of these studies. Other than cholinergic mechanisms are also determined as well as behavioral studies. For all mentioned techniques, examples of results are given. Using this approach, it was investigated that more universal action of oximes is possible when two different reactivators are used. Their action is not simple summation but more potentiation. This potentiation was observed in antidotal properties of the mixture (survival) as well as reactivation efficacy in different organs. This approach allows improving current medical countermeasures against nerve agent poisoning. Support: Ministry of Defence (Czech Republic)-MO0 FVZ 0000501. doi:10.1016/j.toxlet.2011.05.428
P1195 Comparison of blood mercury concentrations in hypertensive and normotensive adults A. Bakhtiarian ∗ , A. Mohaghegh, M. Ghazi- Khansari Dept. of Pharmacology, Tehran University of Medical Sciences, Tehran University of Medical Sciences, Iran Purpose: Hypertension is a very common and important disease. There are conflicting reports about mercury, a trace element, in the genesis of hypertension. In this study we examined the relationship between blood mercury levels and hypertension prevalence in a population-based sample of hypertensive and normotensive patients at the Shariati Hospital and the Tehran Heart Center in Tehran, Iran. Methods: A cross sectional sampling of 224 patients, aged 40–80 years, who participated in physical examinations were included in this study. Results of the study: The range of blood mercury levels was 0–39.55 g/dL. The mean blood mercury level of hypertensive patients (10.75 ± 1.23 g/dL) was higher than that of normotensive patients (1.6 ± 1.02 g/dL). There was a significant difference in the mean blood mercury level of normotensive men (1.74 ± 1.56 g/dL) versus that of hypertensive
0.10–0.267; Zn 7.11–21.88 g/g wet weight, respectively. Levels of Cd, Hg, Pb, Ni were not exceeding the corresponding provisional tolerable weekly intake (PTWI) values. For average consumers, target hazard quotient (THQ) values of inorganic As, Cd, Hg, Pb and Ni indicated the absence of health risks through consumption of the fish species analyzed. Cancer risk estimate for inorganic As (5.7 × 10−6 ) from consuming these fish species was lower than 10−5 (acceptable risk). Our results suggest that there is a need for more information on total dietary exposure of inorganic As and supports the importance of speciation analysis for arsenic in seafood for more appropriate risk assessment of inorganic As in fish species. doi:10.1016/j.toxlet.2011.05.426
P1193 Single and combined effects associated with two xenobiotics widely used in intensive aquaculture on European sea bass (Dicentrarchus labrax) M.A. Jerbi 1,∗ , Z. Ouanes 2 , R. besbes 3 , Z. Haouas 4 , L. Achour 1 , A. Kacem 1 1
Unité De Recherche Génome, Diagnostic Immunitaire Et Valorisation, ISBM, Monastir, Tunisia, 2 Marine and Environmental Toxicology, UR 09-03-IPEIS, Sfax University, Sfax, Tunisia, 3 Institut National des Sciences et Technologies de la Mer, Monastir, Tunisia, 4 Laboratoire d’Histologie et de Cytogénétique, Faculté de Médecine de Monastir, Monastir, Tunisia Several chemicals are used in aquaculture to prevent or to treat diseases outbreaks. These substances are mainly administered by two different modes; by prolonged bath or by complexation with the diet. In the case of intensive aquaculture, the most applied by bath chemicals are formaldehyde (FA) 37% and oxytetracycline (OTC). Under therapeutic use, FA 37% is applied prophylactically at 200 ml/m3 , whereas OTC is used curatively at 40 g/m3 . The goal of the present study is to assess adverse effects associated with the European sea bass (D. labrax) exposure to FA37% and OTC under the same conditions being applied in intensive aquaculture systems. To this end the micronuclei (MN) assay was applied in erythrocytic cells to assess their genotoxicity and cytotoxicity. In parallel a histopathological survey and a study of the oxidative status of the liver were also achieved. Our results showed that both tested chemicals presented genotoxic and cytotoxic potential following a time-dependent pattern. Histologically viewing, it was obvious that both FA and OTC have induced sinusoid dilatation and blood congestion. Intensive vacuolisation and focal necrosis were also observed. These results are confirmed by the biochemical analysis where catalase activity and malondialdehyde have shown a significant increase in reference to control (p ≤ 0.05). Captivatingly, the combined treatment induces a cumulative effect particularly well pronounced after 15 days of exposure suggesting the critical hazards associated to FA and OTC when applied or released together. doi:10.1016/j.toxlet.2011.05.427
S119
P1194 Possible approaches to the development of universal cholinesterase reactivator J. Bajgar 1,∗ , J. Kassa 1 , M. Pohanka 2 1
Toxicology, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic, 2 Center of Advanced Studies, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic Based on our knowledge of the mechanism of nerve agents/organophosphates (OP), anticholinergics, cholinesterase reactivators (oximes) and anticonvulsants are used. At present, there is not an universal reactivator able to reactivate AChE inhibited by all nerve agents/OP. Some steps of development of this antidote are described. Literature survey and other information are necessary; after this stage, inhibition/reactivation potency of the nerve agent/reactivator to AChE can be used to characterize the toxic/therapeutic effects (inhibition/reactivation of cholinesterases) followed by determination of the reactivator’s effect in vitro including molecular modelling. As the first information in vivo is simple characterization by toxicity and later on, reactivation potency in vivo and therapeutic efficacy following administration of various antidotes or their combinations is provided. For further studies in vivo, AChE inhibition/reactivation in different tissues are determined. Quantitative histochemical determination of AChE activity allows fine differentiation among various brain structures. Blood levels of nerve agents and antidotes are necessary part of these studies. Other than cholinergic mechanisms are also determined as well as behavioral studies. For all mentioned techniques, examples of results are given. Using this approach, it was investigated that more universal action of oximes is possible when two different reactivators are used. Their action is not simple summation but more potentiation. This potentiation was observed in antidotal properties of the mixture (survival) as well as reactivation efficacy in different organs. This approach allows improving current medical countermeasures against nerve agent poisoning. Support: Ministry of Defence (Czech Republic)-MO0 FVZ 0000501. doi:10.1016/j.toxlet.2011.05.428
P1195 Comparison of blood mercury concentrations in hypertensive and normotensive adults A. Bakhtiarian ∗ , A. Mohaghegh, M. Ghazi- Khansari Dept. of Pharmacology, Tehran University of Medical Sciences, Tehran University of Medical Sciences, Iran Purpose: Hypertension is a very common and important disease. There are conflicting reports about mercury, a trace element, in the genesis of hypertension. In this study we examined the relationship between blood mercury levels and hypertension prevalence in a population-based sample of hypertensive and normotensive patients at the Shariati Hospital and the Tehran Heart Center in Tehran, Iran. Methods: A cross sectional sampling of 224 patients, aged 40–80 years, who participated in physical examinations were included in this study. Results of the study: The range of blood mercury levels was 0–39.55 g/dL. The mean blood mercury level of hypertensive patients (10.75 ± 1.23 g/dL) was higher than that of normotensive patients (1.6 ± 1.02 g/dL). There was a significant difference in the mean blood mercury level of normotensive men (1.74 ± 1.56 g/dL) versus that of hypertensive