- Email: [email protected]
Morphologic and morphometric changes in ovary due to chronic use of methylphenidate in preadolescent female mice
S184
Abstracts / Toxicology Letters 196S (2010) S37–S351
spp. is the pyrrolizidine alkaloid monocrotaline (MCT). MCT is activated in the liver to the active form (monocrotaline pyrrole). The lung is the primary target to MCT toxic effects and also induces right ventricular failure confirmed by the presence of ascites, pericardial, or pleural effusions. However, the actual cause of death by MCT is not completely understood, particularly during perinatal periods. The aim of the present study was to evaluate the effects of prenatal exposure to low doses of MCT on behavioral and physical development of rat offspring. MCT was isolated of C. spectabilis (0.23% yield). Pregnant rats from the experimental group were treated, by gavage, with 1.0, 3.5 and 7.0 mg/kg of MCT from day 6 to 20 of gestation; the control group received only water. Total body weight gain, water and food consumption were measured in mothers during the experimental period. After the birth, the offspring were examined for the weight and the physical, behavior and reflexology development. The data show a reduced number of pups born in a dose-MCT dependent way. No significant differences between the experimental and controls dams in the weight gain, food consumption and water intake during the pregnancy. Prenatal exposure to MCT did not affect the offspring body weight, motor activity (openfield behaviors), the physical (pinna detachment, eruption of incisor teeth, eye opening, testes descent, coat appearance, ears open and vaginal opening) and reflexologic development (palmar grasp, negative geotaxis and adult gait). Therefore, the present study suggests that prenatal MCT exposure did not induce physical and neurodevelopmental disruption of pup rats, but reduce the pup number. This effect was probably a consequence of MCT maternal toxicity. doi:10.1016/j.toxlet.2010.03.626
P204-003 Embryoprotective role of constitutive antioxidative catalase in wild-type and acatalasemic mice in vivo and in embryo culture J. Perstin, P.G. Wells University of Toronto, Canada Low embryonic activities of antioxidative enzymes including catalase, which detoxifies hydrogen peroxide (H2 O2 ), may leave the embryo susceptible to embryopathic effects of endogenous reactive oxygen species (ROS) or ROS enhancement by xenobiotics like the antiepileptic drug phenytoin. Although protein therapy with exogenous catalase reduces phenytoin teratogenicity in mice, little is known about the embryoprotective importance of the endogenous enzyme. Herein we investigated the in vitro and in vivo protective importance of constitutive catalase in wildtype (C3HeB/FeJ) and mutant catalase-deficient (acatalasemic) (C3Ga.Cg-Catb/J) mice. In embryo culture, unlike susceptible outbred CD-1 mice, wild-type C3H embryos exposed to phenytoin did not exhibit embryopathies, suggesting strain resistance to this teratogen. In contrast, acatalasemic embryos exposed to phenytoin exhibited enhanced dysmorphogenesis that correlated with lower catalase activity and was completely blocked by catalase protein therapy. Catalase activity in acatalasemic embryos was about half that in wild-type controls, and was not enhanced by phenytoin within the 48-h culture period. In vivo, untreated acatalasemic mice were more susceptible than wild-type controls to both in utero and postnatal death, with a 3-fold greater incidence of resorptions and fetal death, revealing the embryopathic potential of endogenous ROS. As in embryo culture, this strain was resistant to phenytoin teratogenicity, although phenytoin caused a genotypeindependent increase in late fetal death and decreased mean fetal weight. These results provide the first direct evidence that the relatively low level of constitutive embryonic catalase provides
important protection to the developing conceptus. (Support: Canadian Institutes of Health Research) doi:10.1016/j.toxlet.2010.03.627
P204-004 Morphologic and morphometric changes in ovary due to chronic use of methylphenidate in preadolescent female mice S. Fazelipour Tehran Medical Branch, Islamic Azad University, Iran Background: MPH (methylphenidate) is a psychomotor stimulant medication widely used for the treatment of ADHD. Given the extent of prescribed use of MPH, and because MPH interacts with the same brain pathway activated by drugs of abuse. MPH also has adverse effect on several sites like cardiovascular and reproductive system. It also affected growth pattern in children. Method: We use 40 preadolescent female mice in four groups (1 control and 3 experimental). The experimental groups fed with different dosages (2, 5, 10 mg/kg) of their MPH. After puberty, surveyed morphologic and morphometric changes of their ovaries. Result: In MPH fed animals we found that length, width and area of ovaries and body weight differences in animals were significant reduction in compared with control group (P < 0.05). But there were no significant differences between different doses in these parameters. Conclusion: Chronic use of MPH affected the ovary in preadolescent female mice and reduced its diameter like length, width and area. doi:10.1016/j.toxlet.2010.03.628
P204-005 Embryotoxic and teratogenic effects of Roundup® Max on rat development A. Geris¸lio˘glu 1 , C. Güngörmüs¸ 1 , A. Korkmaz 2 , D. Kolankaya 1 Hacettepe University, Turkey, 2 Ministry of Agriculture and Rural Affairs, Turkey
1
Glyphosate is the active ingredient of Roundup® Max, commercially available as a non-selective, organophosphorated agrochemical and broad-spectrum herbicide. It is widely used in many countries, including Turkey to control weeds in emerged grasses, broad-leaf weeds, rice, corn and soy plantations which acts after the sprout in a systemic way. In recent study, to evaluate the possible developmental effects of Glyphosate, female Wistar rats were treated with Roundup® Max containing 78.5% Glyphosate by oral gavage during pregnancy. There were three groups of each containing five pregnant rats. We administrated 10% and 20% doses of Roundup® Max, which is the commercial form of Glyphosate with LD50 dose 5600 mg/kg. Rats in Group I, II and III were fed with standard diet, 560 mg/kg Roundup and 1120 mg/kg Roundup during gestational days (GD 0–20) respectively. We assessed foetal body lengths and weights, organ weights and also made morphometric examination of placenta and umbilical cord. There were a significant decrease in foetal body weights and foetal liver weights in treatment groups (P ≤ 0.05). The placental weights of Group II and Group III were found to be increased statistically. Placental lengths were increased in treatment groups. The umbilical cord lengths in Group II showed a significant increase when compared to Group I. It was evaluated that implantation ratios were decreased and
Abstracts / Toxicology Letters 196S (2010) S37–S351
spp. is the pyrrolizidine alkaloid monocrotaline (MCT). MCT is activated in the liver to the active form (monocrotaline pyrrole). The lung is the primary target to MCT toxic effects and also induces right ventricular failure confirmed by the presence of ascites, pericardial, or pleural effusions. However, the actual cause of death by MCT is not completely understood, particularly during perinatal periods. The aim of the present study was to evaluate the effects of prenatal exposure to low doses of MCT on behavioral and physical development of rat offspring. MCT was isolated of C. spectabilis (0.23% yield). Pregnant rats from the experimental group were treated, by gavage, with 1.0, 3.5 and 7.0 mg/kg of MCT from day 6 to 20 of gestation; the control group received only water. Total body weight gain, water and food consumption were measured in mothers during the experimental period. After the birth, the offspring were examined for the weight and the physical, behavior and reflexology development. The data show a reduced number of pups born in a dose-MCT dependent way. No significant differences between the experimental and controls dams in the weight gain, food consumption and water intake during the pregnancy. Prenatal exposure to MCT did not affect the offspring body weight, motor activity (openfield behaviors), the physical (pinna detachment, eruption of incisor teeth, eye opening, testes descent, coat appearance, ears open and vaginal opening) and reflexologic development (palmar grasp, negative geotaxis and adult gait). Therefore, the present study suggests that prenatal MCT exposure did not induce physical and neurodevelopmental disruption of pup rats, but reduce the pup number. This effect was probably a consequence of MCT maternal toxicity. doi:10.1016/j.toxlet.2010.03.626
P204-003 Embryoprotective role of constitutive antioxidative catalase in wild-type and acatalasemic mice in vivo and in embryo culture J. Perstin, P.G. Wells University of Toronto, Canada Low embryonic activities of antioxidative enzymes including catalase, which detoxifies hydrogen peroxide (H2 O2 ), may leave the embryo susceptible to embryopathic effects of endogenous reactive oxygen species (ROS) or ROS enhancement by xenobiotics like the antiepileptic drug phenytoin. Although protein therapy with exogenous catalase reduces phenytoin teratogenicity in mice, little is known about the embryoprotective importance of the endogenous enzyme. Herein we investigated the in vitro and in vivo protective importance of constitutive catalase in wildtype (C3HeB/FeJ) and mutant catalase-deficient (acatalasemic) (C3Ga.Cg-Catb/J) mice. In embryo culture, unlike susceptible outbred CD-1 mice, wild-type C3H embryos exposed to phenytoin did not exhibit embryopathies, suggesting strain resistance to this teratogen. In contrast, acatalasemic embryos exposed to phenytoin exhibited enhanced dysmorphogenesis that correlated with lower catalase activity and was completely blocked by catalase protein therapy. Catalase activity in acatalasemic embryos was about half that in wild-type controls, and was not enhanced by phenytoin within the 48-h culture period. In vivo, untreated acatalasemic mice were more susceptible than wild-type controls to both in utero and postnatal death, with a 3-fold greater incidence of resorptions and fetal death, revealing the embryopathic potential of endogenous ROS. As in embryo culture, this strain was resistant to phenytoin teratogenicity, although phenytoin caused a genotypeindependent increase in late fetal death and decreased mean fetal weight. These results provide the first direct evidence that the relatively low level of constitutive embryonic catalase provides
important protection to the developing conceptus. (Support: Canadian Institutes of Health Research) doi:10.1016/j.toxlet.2010.03.627
P204-004 Morphologic and morphometric changes in ovary due to chronic use of methylphenidate in preadolescent female mice S. Fazelipour Tehran Medical Branch, Islamic Azad University, Iran Background: MPH (methylphenidate) is a psychomotor stimulant medication widely used for the treatment of ADHD. Given the extent of prescribed use of MPH, and because MPH interacts with the same brain pathway activated by drugs of abuse. MPH also has adverse effect on several sites like cardiovascular and reproductive system. It also affected growth pattern in children. Method: We use 40 preadolescent female mice in four groups (1 control and 3 experimental). The experimental groups fed with different dosages (2, 5, 10 mg/kg) of their MPH. After puberty, surveyed morphologic and morphometric changes of their ovaries. Result: In MPH fed animals we found that length, width and area of ovaries and body weight differences in animals were significant reduction in compared with control group (P < 0.05). But there were no significant differences between different doses in these parameters. Conclusion: Chronic use of MPH affected the ovary in preadolescent female mice and reduced its diameter like length, width and area. doi:10.1016/j.toxlet.2010.03.628
P204-005 Embryotoxic and teratogenic effects of Roundup® Max on rat development A. Geris¸lio˘glu 1 , C. Güngörmüs¸ 1 , A. Korkmaz 2 , D. Kolankaya 1 Hacettepe University, Turkey, 2 Ministry of Agriculture and Rural Affairs, Turkey
1
Glyphosate is the active ingredient of Roundup® Max, commercially available as a non-selective, organophosphorated agrochemical and broad-spectrum herbicide. It is widely used in many countries, including Turkey to control weeds in emerged grasses, broad-leaf weeds, rice, corn and soy plantations which acts after the sprout in a systemic way. In recent study, to evaluate the possible developmental effects of Glyphosate, female Wistar rats were treated with Roundup® Max containing 78.5% Glyphosate by oral gavage during pregnancy. There were three groups of each containing five pregnant rats. We administrated 10% and 20% doses of Roundup® Max, which is the commercial form of Glyphosate with LD50 dose 5600 mg/kg. Rats in Group I, II and III were fed with standard diet, 560 mg/kg Roundup and 1120 mg/kg Roundup during gestational days (GD 0–20) respectively. We assessed foetal body lengths and weights, organ weights and also made morphometric examination of placenta and umbilical cord. There were a significant decrease in foetal body weights and foetal liver weights in treatment groups (P ≤ 0.05). The placental weights of Group II and Group III were found to be increased statistically. Placental lengths were increased in treatment groups. The umbilical cord lengths in Group II showed a significant increase when compared to Group I. It was evaluated that implantation ratios were decreased and