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The teratogenic effects of florazepam intake in rat fetus during pregnancy
S140
Abstracts / Toxicology Letters 172S (2007) S1–S240
particularly musculoskeletal toxicity risk, limits the indications of these drugs in pediatrics. Beside joint toxicity, quinolones may also cause other musculoskeletal adverse effects such as tendinopathy, myopathy, muscle pain and rhabdomyolysis in severe cases. It is also known that quinolones may prolong QT interval and lead to torsades de pointes syndrome. This electrophysiological change suggests that this drug class possibly has a myocard toxicity potential. In this study, we have evaluated the myocardiotoxic potential of ciprofloxacin and ofloxacin, two commonly used quinolone derivatives, comparatively in juvenile rats. Doses of the drugs (25 and 50 mg/kg) were administered to the animals intraperitoneally, two times a day, for 1-week period. At the end of the treatment period, blood samples have collected via cardiac puncture under ether anesthesia and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase isoenzyme MB (CK-MB) and lactate dehydrogenase (LDH) activities were measured to evaluate cardiotoxicity. All measured biochemical parameters of drug treated rats were higher than those of control rats. But the elevation of the assessed parameters for 50 mg/kg ofloxacin was statistically significant (p < 0.05). According to these results, we concluded that when treated intraperitoneally, both drugs have cardiotoxic effect potential being ofloxacin is more potent than ciprofloxacin in juvenile rats. Keywords: Ciprofloxacin; Ofloxacin; Cardiotoxicity doi:10.1016/j.toxlet.2007.05.363 P29 Phospholipase A2 activity in fractions separated from Iranian Vipera Lebetina venom Mehrnoosh Shanaki, Zohreh Amoozgari, Moghgan Noorbehbahani Jundishapoor University, Ahvaz,khoozestan, Iran Objective: Snake venoms are complex mixtures containing many different biologically active proteins and peptides. These proteins are very specific for their molecular targets and stable in vitro and in vivo. Phospholipase A2 (PLA2) is an enzyme which hydrolyses phospholipids at sn-2 position, releasing fatty acids and lysophospholipids. Some venom contains a number of PLA2 isoforms. PLA2s are major components in snake venom. They display a wide range of biological effects including neurotoxic, myotoxic, cytotoxic, edema producing and antitumoral effects.
Vipera Lebetina is one of the most poisonous snakes in Iran. Our studies on the crude venom have demonstrated the existence of PLA2 activity in the suspension of egg yolk substrate. Phospholipase A2 acted on lipoproteins in egg yolk and produced lysolecthin. The produced lysolecthin is able to solubilizing the egg yolk suspension. Methods: The venom of Vipera Lebetina was separated into five fractions, using gel filtration chromatography on sephadex G-100 equilibrated with 20 mM ammonium acetate buffer PH 6.8.These fractions were tested for PLA2 activity. Result and conclusion: This activity was detected in PII and PIII. It was more prominent in PII. The specific activity of PI was about two times higher than that of crude venom. doi:10.1016/j.toxlet.2007.05.364 P30 The teratogenic effects of florazepam intake in rat fetus during pregnancy Nasrin Takzare 1 , Mir-Jamal Hosseini 2 , Azam Bakhtiarian 2 , Alireza Takzare 1 1 Department
of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; 2 Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Florazepam is a long acting drug with sedative, hypnotic, anxiolytic, relaxant, and anti-epileptic properties. This drug is commonly used by adults, including pregnant women, intentionally or sometimes unintentionally during their pregnancy. Therefore, it seems a special problem to the clinician treating anxiety disorder in women. It should be noticed that florazepam consumption during pregnancy may have teratogenic effects on the fetus. In this research, we have studied the teratogenicity of florazepam intake during pregnancy and its effects on fetus development. For this work, About 30 virgin rats of known age and weight were used. After being pregnant, they were divided in three groups: negative and positive control groups, case groups exposed for 1 to 6 mg/kg/day. The fetuses were first studied macroscopically regarding gross anomalies, and then histological and histochemically to exactly inspect the defects of tissue organogenesis. According to the results obtained, there was significant difference in the weight and length of the cases compared to the control group. Several anomalies of the eyes and ears and anomalies of the skull were found. The statistical results indicate that flo-
Abstracts / Toxicology Letters 172S (2007) S1–S240
razepam intake during the second half of pregnancy can lead to irreversible anomalies. Keywords: Teratogenicity; Florazepam; Pregnancy; Visual system defects; Virgin rats doi:10.1016/j.toxlet.2007.05.365 P31 Case report concerning two cases of ergotamine poisoning Maria Toutoudaki 1 , Manolis Tzatzarakis 1 , George Briassoulis 2 , Anna Maria Spanaki 2 , Stamatis Belivanis 3 , Aristidis Tsatsakis 1 1 University
of Crete, Heraklion, Crete, Greece; Hopsital of Heraklion, Heraklion, Crete, Greece; 3 General Hospital of Hania, Hania, Crete, Greece
2 University
Ergotamine is a vasoconstrictor used for the prevention and treatment of migraine. It is part of the ergot family of alkaloids. In the present work we report two cases of ergotamine poisoning, one with a fatal and one with non-fatal outcome. The first case concerns a 22-year-old man who was found dead after intravenous injection of ergotamine. Ergotamine was detected in the urine of the victim at a concentration of 300 ng/ml. The second case concerns a girl who has admitted in the Peadiatrics Intesive Care Unit of the University Hospital of Heraklion, following intoxication with ergotamine pills. Ergotamine was detected in the urine of the girl at a concentration of 230 ng/ml. The analysis of the samples was performed by GC–MS, on a Finnigan Mat ion trap system, equipped with 30 m × 0.25 m × 0.25 mm i.d. AT 5MS column, in SIM mode. doi:10.1016/j.toxlet.2007.05.603 P32 A large decrease in the number of ephedra intoxications and a concomitant increase in the number of amphetamine intoxications: A relation? Agnes van Velzen, Teetske van Gorcum, Antoinette van Riel, Jan Meulenbelt, Irma de Vries National Poisons Information Centre, National Institute for Public Health and the Environment, Bilthoven, Netherlands
S141
Introduction: The Dutch national poisons information centre receives around 37,000 enquiries a year about acute intoxications in humans and animals. One of the drugs that the poisons centre is consulted about is ephedra. Ephedra is a stimulating agent, isolated from ephedra-alkaloids containing plants. Ephedra containing products are used to promote weight loss and to enhance physical and mental achievements. The number of consultations about ephedra was followed from 2001 to 2006. Results: From 2001 to 2004, ephedracontaining products became very popular. The number of reported ephedra intoxications increased from 28 in 2001 to 127 in 2004. Research showed that many ephedra preparations contained higher concentrations of ephedra-alkaloids than indicated on the packaging and that other stimulating agents, like caffeine, were often present in the preparations as well, increasing the risk for toxic effects. Based on these facts, an amendment of the law was passed in February 2004, stating that ephedracontaining products could only be marketed as medicinal products. After 2004, the number of enquiries about ephedra decreased sharply, to only 55 in 2006. However, the number of enquiries about amphetamines used to be around 40 per year. Simultaneously with the decrease in the number of reported ephedra intoxications, the number of reported intoxications with amphetamines increased considerably, to 114 in 2005 and 97 in 2006. Like ephedra, amphetamines can be used to promote weight loss and to enhance achievements. Conclusion: These data suggest that prohibition of selling ephedra preparations may have led to ephedra users switching to amphetamines after 2004. doi:10.1016/j.toxlet.2007.05.604 P7 Immunotoxicology I01 Respiratory allergy induced by the skin allergen DNCB Josje Arts, Jos van Triel, Frieke Kuper TNO Quality of Life, Zeist, Netherlands In REACH, the local lymph node assay (LLNA) is recommended to investigate skin sensitization potential of low molecular weight (LMW) chemicals. Interestingly, respiratory allergens were also positive when topically applied in this model. In addition, experimental evidence in animals and limited evidence in humans suggests that dermal and inhalation exposure to LMW skin allergens can result in airways sensitization. Because of the sys-
Abstracts / Toxicology Letters 172S (2007) S1–S240
particularly musculoskeletal toxicity risk, limits the indications of these drugs in pediatrics. Beside joint toxicity, quinolones may also cause other musculoskeletal adverse effects such as tendinopathy, myopathy, muscle pain and rhabdomyolysis in severe cases. It is also known that quinolones may prolong QT interval and lead to torsades de pointes syndrome. This electrophysiological change suggests that this drug class possibly has a myocard toxicity potential. In this study, we have evaluated the myocardiotoxic potential of ciprofloxacin and ofloxacin, two commonly used quinolone derivatives, comparatively in juvenile rats. Doses of the drugs (25 and 50 mg/kg) were administered to the animals intraperitoneally, two times a day, for 1-week period. At the end of the treatment period, blood samples have collected via cardiac puncture under ether anesthesia and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase isoenzyme MB (CK-MB) and lactate dehydrogenase (LDH) activities were measured to evaluate cardiotoxicity. All measured biochemical parameters of drug treated rats were higher than those of control rats. But the elevation of the assessed parameters for 50 mg/kg ofloxacin was statistically significant (p < 0.05). According to these results, we concluded that when treated intraperitoneally, both drugs have cardiotoxic effect potential being ofloxacin is more potent than ciprofloxacin in juvenile rats. Keywords: Ciprofloxacin; Ofloxacin; Cardiotoxicity doi:10.1016/j.toxlet.2007.05.363 P29 Phospholipase A2 activity in fractions separated from Iranian Vipera Lebetina venom Mehrnoosh Shanaki, Zohreh Amoozgari, Moghgan Noorbehbahani Jundishapoor University, Ahvaz,khoozestan, Iran Objective: Snake venoms are complex mixtures containing many different biologically active proteins and peptides. These proteins are very specific for their molecular targets and stable in vitro and in vivo. Phospholipase A2 (PLA2) is an enzyme which hydrolyses phospholipids at sn-2 position, releasing fatty acids and lysophospholipids. Some venom contains a number of PLA2 isoforms. PLA2s are major components in snake venom. They display a wide range of biological effects including neurotoxic, myotoxic, cytotoxic, edema producing and antitumoral effects.
Vipera Lebetina is one of the most poisonous snakes in Iran. Our studies on the crude venom have demonstrated the existence of PLA2 activity in the suspension of egg yolk substrate. Phospholipase A2 acted on lipoproteins in egg yolk and produced lysolecthin. The produced lysolecthin is able to solubilizing the egg yolk suspension. Methods: The venom of Vipera Lebetina was separated into five fractions, using gel filtration chromatography on sephadex G-100 equilibrated with 20 mM ammonium acetate buffer PH 6.8.These fractions were tested for PLA2 activity. Result and conclusion: This activity was detected in PII and PIII. It was more prominent in PII. The specific activity of PI was about two times higher than that of crude venom. doi:10.1016/j.toxlet.2007.05.364 P30 The teratogenic effects of florazepam intake in rat fetus during pregnancy Nasrin Takzare 1 , Mir-Jamal Hosseini 2 , Azam Bakhtiarian 2 , Alireza Takzare 1 1 Department
of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; 2 Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Florazepam is a long acting drug with sedative, hypnotic, anxiolytic, relaxant, and anti-epileptic properties. This drug is commonly used by adults, including pregnant women, intentionally or sometimes unintentionally during their pregnancy. Therefore, it seems a special problem to the clinician treating anxiety disorder in women. It should be noticed that florazepam consumption during pregnancy may have teratogenic effects on the fetus. In this research, we have studied the teratogenicity of florazepam intake during pregnancy and its effects on fetus development. For this work, About 30 virgin rats of known age and weight were used. After being pregnant, they were divided in three groups: negative and positive control groups, case groups exposed for 1 to 6 mg/kg/day. The fetuses were first studied macroscopically regarding gross anomalies, and then histological and histochemically to exactly inspect the defects of tissue organogenesis. According to the results obtained, there was significant difference in the weight and length of the cases compared to the control group. Several anomalies of the eyes and ears and anomalies of the skull were found. The statistical results indicate that flo-
Abstracts / Toxicology Letters 172S (2007) S1–S240
razepam intake during the second half of pregnancy can lead to irreversible anomalies. Keywords: Teratogenicity; Florazepam; Pregnancy; Visual system defects; Virgin rats doi:10.1016/j.toxlet.2007.05.365 P31 Case report concerning two cases of ergotamine poisoning Maria Toutoudaki 1 , Manolis Tzatzarakis 1 , George Briassoulis 2 , Anna Maria Spanaki 2 , Stamatis Belivanis 3 , Aristidis Tsatsakis 1 1 University
of Crete, Heraklion, Crete, Greece; Hopsital of Heraklion, Heraklion, Crete, Greece; 3 General Hospital of Hania, Hania, Crete, Greece
2 University
Ergotamine is a vasoconstrictor used for the prevention and treatment of migraine. It is part of the ergot family of alkaloids. In the present work we report two cases of ergotamine poisoning, one with a fatal and one with non-fatal outcome. The first case concerns a 22-year-old man who was found dead after intravenous injection of ergotamine. Ergotamine was detected in the urine of the victim at a concentration of 300 ng/ml. The second case concerns a girl who has admitted in the Peadiatrics Intesive Care Unit of the University Hospital of Heraklion, following intoxication with ergotamine pills. Ergotamine was detected in the urine of the girl at a concentration of 230 ng/ml. The analysis of the samples was performed by GC–MS, on a Finnigan Mat ion trap system, equipped with 30 m × 0.25 m × 0.25 mm i.d. AT 5MS column, in SIM mode. doi:10.1016/j.toxlet.2007.05.603 P32 A large decrease in the number of ephedra intoxications and a concomitant increase in the number of amphetamine intoxications: A relation? Agnes van Velzen, Teetske van Gorcum, Antoinette van Riel, Jan Meulenbelt, Irma de Vries National Poisons Information Centre, National Institute for Public Health and the Environment, Bilthoven, Netherlands
S141
Introduction: The Dutch national poisons information centre receives around 37,000 enquiries a year about acute intoxications in humans and animals. One of the drugs that the poisons centre is consulted about is ephedra. Ephedra is a stimulating agent, isolated from ephedra-alkaloids containing plants. Ephedra containing products are used to promote weight loss and to enhance physical and mental achievements. The number of consultations about ephedra was followed from 2001 to 2006. Results: From 2001 to 2004, ephedracontaining products became very popular. The number of reported ephedra intoxications increased from 28 in 2001 to 127 in 2004. Research showed that many ephedra preparations contained higher concentrations of ephedra-alkaloids than indicated on the packaging and that other stimulating agents, like caffeine, were often present in the preparations as well, increasing the risk for toxic effects. Based on these facts, an amendment of the law was passed in February 2004, stating that ephedracontaining products could only be marketed as medicinal products. After 2004, the number of enquiries about ephedra decreased sharply, to only 55 in 2006. However, the number of enquiries about amphetamines used to be around 40 per year. Simultaneously with the decrease in the number of reported ephedra intoxications, the number of reported intoxications with amphetamines increased considerably, to 114 in 2005 and 97 in 2006. Like ephedra, amphetamines can be used to promote weight loss and to enhance achievements. Conclusion: These data suggest that prohibition of selling ephedra preparations may have led to ephedra users switching to amphetamines after 2004. doi:10.1016/j.toxlet.2007.05.604 P7 Immunotoxicology I01 Respiratory allergy induced by the skin allergen DNCB Josje Arts, Jos van Triel, Frieke Kuper TNO Quality of Life, Zeist, Netherlands In REACH, the local lymph node assay (LLNA) is recommended to investigate skin sensitization potential of low molecular weight (LMW) chemicals. Interestingly, respiratory allergens were also positive when topically applied in this model. In addition, experimental evidence in animals and limited evidence in humans suggests that dermal and inhalation exposure to LMW skin allergens can result in airways sensitization. Because of the sys-