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Retrospective evaluation of the drug use in pregnancy in Manisa
Abstracts / Reproductive Toxicology 48 (2014) 23–36
P-5 Immunoexpression of bone morphogenetic proteins in rat skeleton was not affected by in-utero exposure to cyclooxygenase inhibitors F. Burdan 1,2,∗ , A. Wrona 2 , R. Klepacz 3 , W. Dworzanski 1 , M. Cendrowska-Pinkosz 1 , A. Dworzanska 1 , T. Hermanowicz-Dryka 1 , W. Wrona 4 , J. Szumilo 3 1
Department of Human Anatomy, Medical University of Lublin, Poland 2 St. John’s Cancer Center, Lublin, Poland 3 Department of Clinical Pathomorphology, Medical University of Lublin, Poland 4 3rd Department of Gynecology, Medical University of Lublin, Poland Introduction: Animal data indicates that cyclooxygenase (COX) inhibitors, also known as non-steroidal anti-inflammatory drugs (NSAID), may induce various congenital anomalies, including skeletal developmental variations. The aim of the study was to evaluate effects of non-selective (piroxicam) and selective COX-2 inhibitors (DFU – 5-dimethyl-3-(3-fluorophenyl)-4-(4methylsulfonyl) phenyl-2(5H)-furanone) on immunoexpression of bone morphogenetic proteins (BMP). Materials: Piroxicam (0.3, 1.5 and 3 mg/kg/dose) and DFU (0.2, 2.0 and 20.0 mg/kg/dose) were administered once daily to pregnant Wistar CRL:(WI)WUBR rats from the 8 gestational day until the 7 locational day. Females were giving birth naturally and on 7th day of lactation newborns were sacrificed. The limbs of the male pups were separated, fixed and routinely processed into paraffin blocks. Immunohistochemical reactions using antibodies against BMP-2, BMP-4 and BMP-6 were performed. Results: Morphology of joints, cartilaginous and ossified skeletal structures as well as immunoreactivity of BMPs was not disturbed in evaluated animals. The incidence of minimal, occasionally observed developmental abnormalities (i.e. chondrocytes irregularities in epiphyseal cartilage) was similar between control and drug-exposed groups. Conclusions: Piroxicam and DFU did not affect development of distinguished and accessory structures of synovial joint and epiphyseal cartilage in rats when administered in-utero and to nursing dams. http://dx.doi.org/10.1016/j.reprotox.2014.07.033 P-6 Alterations in the reproductive performance of the female rats and fetotoxicity of Lentinula edodes (Shiitake) Ítalo Frizo ∗ , Thaisa B. Pickler, Denise Grotto, Marli Gerenutti Laboratory for the Toxicological Research (Lapetox), University of Sorocaba, Sorocaba, São Paulo, Brazil Introduction: The Lentinula edodes mushroom, popularly known as Shiitake, is attracting the attention of scientists all over the world nowadays due to the high quantity of beta-glucans and phenols in its composition. It presents potent antitumor and anti-inflammatory actions among several other medical effects, including dyslipidemia treatment. It is also used worldwide as food supplement. The present study was performed to investigate the effects of L. edodes consumption in a rat reproduction model, focusing on safety during pregnancy.
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Methods: Pregnant rats received orally reconstituted powderdehydrated L. edodes mushroom (0.53 g beta-glucans per 100 g of mushroom; 2.4 mg GAE/g of phenolic compounds) at daily doses of 400 mg/kg and 800 mg/kg (portions based on daily human consumption) from the first to the twentieth day of gestation; a saline solution was administered to the control group. The fetuses were removed on the twenty-first day by caesarean section. Maternal kidney and liver toxicity were assessed and oxidative stress was measured by GSH. The corpora lutea, implantations, resorptions, live and dead fetuses were counted. The placentae and fetuses were weighed. External and visceral morphology examinations of fetuses were performed following Bodian fixation, whereas skeletal analysis was carried out following diaphanization and staining with alizarin red-S. Results: L. edodes reduced the glutathione (GHS) plasma ratio. No changes were observed in urea plasma ratio, creatinine, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). There was an increase in post implantation loss, reduced body weight and external measurements of fetuses. No other visceral or skeletal abnormalities of the fetuses were noted. Conclusion: L. edodes was shown to have antioxidant properties in the pregnant rat at doses of 400 mg/kg/day and 800 mg/kg/day; despite a lack of maternal toxicity, effects on reproductive performance and fetal toxicity were observed. http://dx.doi.org/10.1016/j.reprotox.2014.07.034 P-7 Retrospective evaluation of the drug use in pregnancy in Manisa Tugba Gurpinar ∗ , Kamil Vural, Bedirhan Ay, Gulay Yıldırım, Ercument Olmez Celal Bayar University, Department of Pharmacology, Manisa, Turkey Introduction: Drug use in pregnancy is a very important issue due to potential teratogenic effects. It is important to consider the risks and benefits of drug therapy to both mother and fetus. Regarding teratogenic effects, the greatest risk is considered to be between the first and eighth week of pregnancy. There are limited studies regarding drug use during pregnancy in Turkey. Methods: This study was performed at Pharmacology Department of the Celal Bayar University Hospital in Manisa, Turkey. The drugs were evaluated according the statement from the patient. Pregnancies between the years 2010 and 2014 with drug use during any week of gestation were retrospectively evaluated. Results: The most frequent drug categories used in Manisa were antidepressants, antibiotics, analgesics and antiepileptics, respectively. Antihistamines, muscle relaxants, respiratory system drugs were also among the commonly used drugs. Drugs were grouped according to Food and Drug Administration (FDA) pregnancy classification, which has been frequently used in our country. Pregnant women received drugs of FDA groups C, D, B, and X, respectively. Conclusions: Patients were found to be more likely to consult a doctor in first three months during pregnancy. It is important to raise awareness about birth control and educate women about medication during a possible pregnancy. Questioning about pregnancy before prescribing drugs will lower the risk of teratogenity. http://dx.doi.org/10.1016/j.reprotox.2014.07.035
P-5 Immunoexpression of bone morphogenetic proteins in rat skeleton was not affected by in-utero exposure to cyclooxygenase inhibitors F. Burdan 1,2,∗ , A. Wrona 2 , R. Klepacz 3 , W. Dworzanski 1 , M. Cendrowska-Pinkosz 1 , A. Dworzanska 1 , T. Hermanowicz-Dryka 1 , W. Wrona 4 , J. Szumilo 3 1
Department of Human Anatomy, Medical University of Lublin, Poland 2 St. John’s Cancer Center, Lublin, Poland 3 Department of Clinical Pathomorphology, Medical University of Lublin, Poland 4 3rd Department of Gynecology, Medical University of Lublin, Poland Introduction: Animal data indicates that cyclooxygenase (COX) inhibitors, also known as non-steroidal anti-inflammatory drugs (NSAID), may induce various congenital anomalies, including skeletal developmental variations. The aim of the study was to evaluate effects of non-selective (piroxicam) and selective COX-2 inhibitors (DFU – 5-dimethyl-3-(3-fluorophenyl)-4-(4methylsulfonyl) phenyl-2(5H)-furanone) on immunoexpression of bone morphogenetic proteins (BMP). Materials: Piroxicam (0.3, 1.5 and 3 mg/kg/dose) and DFU (0.2, 2.0 and 20.0 mg/kg/dose) were administered once daily to pregnant Wistar CRL:(WI)WUBR rats from the 8 gestational day until the 7 locational day. Females were giving birth naturally and on 7th day of lactation newborns were sacrificed. The limbs of the male pups were separated, fixed and routinely processed into paraffin blocks. Immunohistochemical reactions using antibodies against BMP-2, BMP-4 and BMP-6 were performed. Results: Morphology of joints, cartilaginous and ossified skeletal structures as well as immunoreactivity of BMPs was not disturbed in evaluated animals. The incidence of minimal, occasionally observed developmental abnormalities (i.e. chondrocytes irregularities in epiphyseal cartilage) was similar between control and drug-exposed groups. Conclusions: Piroxicam and DFU did not affect development of distinguished and accessory structures of synovial joint and epiphyseal cartilage in rats when administered in-utero and to nursing dams. http://dx.doi.org/10.1016/j.reprotox.2014.07.033 P-6 Alterations in the reproductive performance of the female rats and fetotoxicity of Lentinula edodes (Shiitake) Ítalo Frizo ∗ , Thaisa B. Pickler, Denise Grotto, Marli Gerenutti Laboratory for the Toxicological Research (Lapetox), University of Sorocaba, Sorocaba, São Paulo, Brazil Introduction: The Lentinula edodes mushroom, popularly known as Shiitake, is attracting the attention of scientists all over the world nowadays due to the high quantity of beta-glucans and phenols in its composition. It presents potent antitumor and anti-inflammatory actions among several other medical effects, including dyslipidemia treatment. It is also used worldwide as food supplement. The present study was performed to investigate the effects of L. edodes consumption in a rat reproduction model, focusing on safety during pregnancy.
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Methods: Pregnant rats received orally reconstituted powderdehydrated L. edodes mushroom (0.53 g beta-glucans per 100 g of mushroom; 2.4 mg GAE/g of phenolic compounds) at daily doses of 400 mg/kg and 800 mg/kg (portions based on daily human consumption) from the first to the twentieth day of gestation; a saline solution was administered to the control group. The fetuses were removed on the twenty-first day by caesarean section. Maternal kidney and liver toxicity were assessed and oxidative stress was measured by GSH. The corpora lutea, implantations, resorptions, live and dead fetuses were counted. The placentae and fetuses were weighed. External and visceral morphology examinations of fetuses were performed following Bodian fixation, whereas skeletal analysis was carried out following diaphanization and staining with alizarin red-S. Results: L. edodes reduced the glutathione (GHS) plasma ratio. No changes were observed in urea plasma ratio, creatinine, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). There was an increase in post implantation loss, reduced body weight and external measurements of fetuses. No other visceral or skeletal abnormalities of the fetuses were noted. Conclusion: L. edodes was shown to have antioxidant properties in the pregnant rat at doses of 400 mg/kg/day and 800 mg/kg/day; despite a lack of maternal toxicity, effects on reproductive performance and fetal toxicity were observed. http://dx.doi.org/10.1016/j.reprotox.2014.07.034 P-7 Retrospective evaluation of the drug use in pregnancy in Manisa Tugba Gurpinar ∗ , Kamil Vural, Bedirhan Ay, Gulay Yıldırım, Ercument Olmez Celal Bayar University, Department of Pharmacology, Manisa, Turkey Introduction: Drug use in pregnancy is a very important issue due to potential teratogenic effects. It is important to consider the risks and benefits of drug therapy to both mother and fetus. Regarding teratogenic effects, the greatest risk is considered to be between the first and eighth week of pregnancy. There are limited studies regarding drug use during pregnancy in Turkey. Methods: This study was performed at Pharmacology Department of the Celal Bayar University Hospital in Manisa, Turkey. The drugs were evaluated according the statement from the patient. Pregnancies between the years 2010 and 2014 with drug use during any week of gestation were retrospectively evaluated. Results: The most frequent drug categories used in Manisa were antidepressants, antibiotics, analgesics and antiepileptics, respectively. Antihistamines, muscle relaxants, respiratory system drugs were also among the commonly used drugs. Drugs were grouped according to Food and Drug Administration (FDA) pregnancy classification, which has been frequently used in our country. Pregnant women received drugs of FDA groups C, D, B, and X, respectively. Conclusions: Patients were found to be more likely to consult a doctor in first three months during pregnancy. It is important to raise awareness about birth control and educate women about medication during a possible pregnancy. Questioning about pregnancy before prescribing drugs will lower the risk of teratogenity. http://dx.doi.org/10.1016/j.reprotox.2014.07.035