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Atropine but not methylatropine corrects paraoxon-induced respiratory disturbances
S168
Abstracts / Toxicology Letters 180S (2008) S32–S246
of mucosa and further symptoms. By morphometric measurement there was found out, that in parenchyma of testes in experimental animals in comparison with control group occurred decrease of relative volume of seminiferous epithelium about 27% and at the same time increase of relative volume of interstitial tissue. In the experimental group also the average thickness of seminiferous tubules decreased to 250.22 ± 21.9 m in comparison with control group (343.76 ± 27.5 m). Differences were significant (P < 0.01). Disorders of spermiogenesis showed a great variability. Most frequently was damaged zone of meiosis and metamorphosis; in some cases the aspermatic tubules were found. Damage of testicular parenchyma and spermiogenesis negatively influenced also fertility of males (decreasing from 100% at the beginning of experiment to 22.2% at the end of experiment). doi:10.1016/j.toxlet.2008.06.266 S13 Atropine but not methylatropine corrects paraoxon-induced respiratory disturbances Pascal Houzé ∗ , Laetitia Pronzola, Maya Kayouka, Fréderic Baud INSERM U705, Paris, France Objective: Diethylparaoxon (PO) induces respiratory toxicity but the mechanism is still unclear. We previously showed that atropine (A) induced a complete correction of the respiratory toxicity. The aim of this study was to compare the effects of A and methylatropine to clarify the origin of the respiratory toxicity. Methods: Male Sprague–Dawley rats were given PO (0.215 mg kg−1 , sc) and treated with A (base: 10 mg kg−1 , sc) or equimolar MeA (base: 5.42, 54.2, and 542 mg kg−1 , sc) 30 min after PO. Respiratory function was assessed using whole body plethysmography and central temperature using infra-red telemetry. Results are expressed as mean ± S.E.M. Statistical analysis used ANOVA tests. Results: PO induced a significant decrease in temperature 30 min after injection lasting 90 min. This effect was partially corrected by A, but not by MeA. PO induced an increase in expiratory time and tidal volume, and a decrease in respiratory rate. Comparing the effects of equimolar doses, A completely reversed the PO-induced respiratory alterations while MeA had no significant effect. Using 10 and 100-fold higher dosages, MeA still had no significant effect. Discussion: In contrast with A which can cross the blood-brain barrier and modify both peripheral and central muscarinic effects, MeA does not cross the blood-brain barrier. PO poisoning induced hypothermia was partially corrected by A but not by MeA. A completely reversed respiratory disturbances, while MeA had no significant effect at any dosages. We conclude that PO respiratory toxicity is primarily mediated by disrupted muscarinic signaling in the central nervous system. doi:10.1016/j.toxlet.2008.06.267 S14 TEA pretreatment induces significant increasing of pralidoxime antidotal activity Pascal
Houzé ∗ ,
Maya Kayouka, Patricia Risède, Frédéric Baud
fies the pharmacokinetics of PRX, increasing the beta half-life and decreasing the clearance without modification of the volume of distribution. The aim of this study is to determine if TEA-delayed PRX elimination modify the oxime antidotal activity regarding the diethylparaoxon-induced respiratory effects. Methods: Male Sprague–Dawley rats were intoxicated with diethylparaoxon (PO) (50% of DL50 , SC). Tetraethylammonium (75 mg/kg IM) and PRX (50 mg/kg, IM) were injected 15 and 30 min after PO administration, respectively. Respiratory function was assessed using whole body plethysmography. Results are expressed as mean ± S.E.M. Statistical analysis used Student’s t test and ANOVA tests with p < 0.05. Results: Compared to control group, PO administration induced a significant decrease in respiratory rate, an increase in expiratory time and the tidal volume with no modifications of the inspiratory time. The effects were maximal 30 min post PO and plateaued through the study. At the maximal PO effects, PRX injection induced a rapid (<5 min), complete but transient (<30 min) reversal of paraoxon-induced respiratory effects. In TEA-pretreated group, PRX induced a complete and prolonged (180 min) reversion of all respiratory effects. Conclusion: This preliminary study shows that the decreasing of PRX elimination enhances and prolongs its antidotal activity. This result proves the necessity to maintain high plasma PRX concentrations during organophosphate poisoning therapy. doi:10.1016/j.toxlet.2008.06.268 S15 Extraction and identification of Aldicarb (Temik) from postmortem tissues samples khaled Ibrahim 1,∗ , Madiha Elmoty 3
Zakhary 2 , Abd-Elmonem 3 , Abd-
1 Forensic chemist at Assuit Chemical Laboratory of Medico-legal Department, Ministry of Justice, Egypt, 2 Biochemistry Department, Faculty of Medicine, Assiut University, Assiut 71516, Egypt, 3 Head of Assiut Chemical Laboratory, Medico-legal Department, Ministry of Justice, Egypt
Keywords: Temik; Tissue sample; TLC and HPLC Aldicarb is a potent inhibitor of cholinesterase and has a high acute toxicity. This means that it acts as a nerve poison by disrupting nerve impulses. In this submitted work, the extraction and identification of Temik in stomach content from autopsy cases. The analytical protocol includes grinding these tissues with dichloromethane at pH 5.7. The reaction products was tested by T.L.C. on silica gel precoated plates and dichloromethane:ethyl acetate:chloroform (65:25:10) mobile phase, a violet spots are formed after irradiation by U.V. light. Also, colored spots appear when sprayed by Dragen droff or furfural reagents. This was the method has been confirmed by sharp peak by HPLC measurement. doi:10.1016/j.toxlet.2008.06.269 S16 Roles of detoxification enzymes in pyrethroid resistance of Helicoverpa armigera from Turkey
INSERM U705, Paris, France
Metin Konus 1,∗ , Sakine Ugurlu 2 , Mesude Iscan 3
Objective: The efficiency of pralidoxime methylsulfate (PRX), used as an antidote to organophosphate poisoning is depends on its plasma concentrations. In rats, we have previously shown that a pretreatment by tetraethylammonium (TEA) significantly modi-
1
Graduate Program of Biochemistry, Middle East Technical University, Ankara, Turkey, 2 Plant Protection Central Research Institute, Ankara, Turkey, 3 Department of Biological Sciences, Middle East Technical University, Ankara, Turkey
Abstracts / Toxicology Letters 180S (2008) S32–S246
of mucosa and further symptoms. By morphometric measurement there was found out, that in parenchyma of testes in experimental animals in comparison with control group occurred decrease of relative volume of seminiferous epithelium about 27% and at the same time increase of relative volume of interstitial tissue. In the experimental group also the average thickness of seminiferous tubules decreased to 250.22 ± 21.9 m in comparison with control group (343.76 ± 27.5 m). Differences were significant (P < 0.01). Disorders of spermiogenesis showed a great variability. Most frequently was damaged zone of meiosis and metamorphosis; in some cases the aspermatic tubules were found. Damage of testicular parenchyma and spermiogenesis negatively influenced also fertility of males (decreasing from 100% at the beginning of experiment to 22.2% at the end of experiment). doi:10.1016/j.toxlet.2008.06.266 S13 Atropine but not methylatropine corrects paraoxon-induced respiratory disturbances Pascal Houzé ∗ , Laetitia Pronzola, Maya Kayouka, Fréderic Baud INSERM U705, Paris, France Objective: Diethylparaoxon (PO) induces respiratory toxicity but the mechanism is still unclear. We previously showed that atropine (A) induced a complete correction of the respiratory toxicity. The aim of this study was to compare the effects of A and methylatropine to clarify the origin of the respiratory toxicity. Methods: Male Sprague–Dawley rats were given PO (0.215 mg kg−1 , sc) and treated with A (base: 10 mg kg−1 , sc) or equimolar MeA (base: 5.42, 54.2, and 542 mg kg−1 , sc) 30 min after PO. Respiratory function was assessed using whole body plethysmography and central temperature using infra-red telemetry. Results are expressed as mean ± S.E.M. Statistical analysis used ANOVA tests. Results: PO induced a significant decrease in temperature 30 min after injection lasting 90 min. This effect was partially corrected by A, but not by MeA. PO induced an increase in expiratory time and tidal volume, and a decrease in respiratory rate. Comparing the effects of equimolar doses, A completely reversed the PO-induced respiratory alterations while MeA had no significant effect. Using 10 and 100-fold higher dosages, MeA still had no significant effect. Discussion: In contrast with A which can cross the blood-brain barrier and modify both peripheral and central muscarinic effects, MeA does not cross the blood-brain barrier. PO poisoning induced hypothermia was partially corrected by A but not by MeA. A completely reversed respiratory disturbances, while MeA had no significant effect at any dosages. We conclude that PO respiratory toxicity is primarily mediated by disrupted muscarinic signaling in the central nervous system. doi:10.1016/j.toxlet.2008.06.267 S14 TEA pretreatment induces significant increasing of pralidoxime antidotal activity Pascal
Houzé ∗ ,
Maya Kayouka, Patricia Risède, Frédéric Baud
fies the pharmacokinetics of PRX, increasing the beta half-life and decreasing the clearance without modification of the volume of distribution. The aim of this study is to determine if TEA-delayed PRX elimination modify the oxime antidotal activity regarding the diethylparaoxon-induced respiratory effects. Methods: Male Sprague–Dawley rats were intoxicated with diethylparaoxon (PO) (50% of DL50 , SC). Tetraethylammonium (75 mg/kg IM) and PRX (50 mg/kg, IM) were injected 15 and 30 min after PO administration, respectively. Respiratory function was assessed using whole body plethysmography. Results are expressed as mean ± S.E.M. Statistical analysis used Student’s t test and ANOVA tests with p < 0.05. Results: Compared to control group, PO administration induced a significant decrease in respiratory rate, an increase in expiratory time and the tidal volume with no modifications of the inspiratory time. The effects were maximal 30 min post PO and plateaued through the study. At the maximal PO effects, PRX injection induced a rapid (<5 min), complete but transient (<30 min) reversal of paraoxon-induced respiratory effects. In TEA-pretreated group, PRX induced a complete and prolonged (180 min) reversion of all respiratory effects. Conclusion: This preliminary study shows that the decreasing of PRX elimination enhances and prolongs its antidotal activity. This result proves the necessity to maintain high plasma PRX concentrations during organophosphate poisoning therapy. doi:10.1016/j.toxlet.2008.06.268 S15 Extraction and identification of Aldicarb (Temik) from postmortem tissues samples khaled Ibrahim 1,∗ , Madiha Elmoty 3
Zakhary 2 , Abd-Elmonem 3 , Abd-
1 Forensic chemist at Assuit Chemical Laboratory of Medico-legal Department, Ministry of Justice, Egypt, 2 Biochemistry Department, Faculty of Medicine, Assiut University, Assiut 71516, Egypt, 3 Head of Assiut Chemical Laboratory, Medico-legal Department, Ministry of Justice, Egypt
Keywords: Temik; Tissue sample; TLC and HPLC Aldicarb is a potent inhibitor of cholinesterase and has a high acute toxicity. This means that it acts as a nerve poison by disrupting nerve impulses. In this submitted work, the extraction and identification of Temik in stomach content from autopsy cases. The analytical protocol includes grinding these tissues with dichloromethane at pH 5.7. The reaction products was tested by T.L.C. on silica gel precoated plates and dichloromethane:ethyl acetate:chloroform (65:25:10) mobile phase, a violet spots are formed after irradiation by U.V. light. Also, colored spots appear when sprayed by Dragen droff or furfural reagents. This was the method has been confirmed by sharp peak by HPLC measurement. doi:10.1016/j.toxlet.2008.06.269 S16 Roles of detoxification enzymes in pyrethroid resistance of Helicoverpa armigera from Turkey
INSERM U705, Paris, France
Metin Konus 1,∗ , Sakine Ugurlu 2 , Mesude Iscan 3
Objective: The efficiency of pralidoxime methylsulfate (PRX), used as an antidote to organophosphate poisoning is depends on its plasma concentrations. In rats, we have previously shown that a pretreatment by tetraethylammonium (TEA) significantly modi-
1
Graduate Program of Biochemistry, Middle East Technical University, Ankara, Turkey, 2 Plant Protection Central Research Institute, Ankara, Turkey, 3 Department of Biological Sciences, Middle East Technical University, Ankara, Turkey