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Investigation of direct toxic and teratogenic effects of anticoagulants on rat embryonic development using in vitro culture method and genotoxicity assay.
Anat Histol Embryol. 2006 Apr; 35(2):84-92.AH

Abstract

Heparin and low molecular weight heparins (LMWHs) are used to reduce the incidence of venous thromboembolism in pregnancy. Although, these agents have been shown to be safe when used during pregnancy, the studies about direct toxic and teratogenic effects of these drugs on embryonic development are limited. In this study, the effects of heparin and LMWHs on rat embryonic development were investigated by using in vitro embryo culture and micronucleus (MN) assay methods. Rat embryos were cultured in vitro in the presence of different concentrations of heparin (5-40 IU/ml), dalteparin (2.5-20 IU/ml), enoxaparin (25-100 microg/ml) and nadroparin (1-4 IU/ml). Effects of anticoagulants on embryonic developmental parameters were compared and embryos were evaluated for the presence of any malformations. After culturing the embryos, classic MN assay was performed. Anticoagulants significantly decreased all growth and developmental parameters dose-dependently. Dalteparin and enoxaparin were found to cause more developmental toxicity than heparin and nadroparin. Along with haematoma in general, heparin and nadroparin caused maxillary deformity, situs inversus and oedema most frequently, while neural tube defects were observed with dalteparin and enoxaparin. All agents also significantly induced MN formation in rat embryonic blood cells. These results indicate the possible genotoxic effects of anticoagulant agents on the developing rat embryo when applied directly.

Authors+Show Affiliations

Department of Anatomy, Meram Medical Faculty, Selcuk University, 42080 Konya, Turkey.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16542172

Citation

Uysal, I I., et al. "Investigation of Direct Toxic and Teratogenic Effects of Anticoagulants On Rat Embryonic Development Using in Vitro Culture Method and Genotoxicity Assay." Anatomia, Histologia, Embryologia, vol. 35, no. 2, 2006, pp. 84-92.
Uysal II, Karabulut AK, Ozdemir K, et al. Investigation of direct toxic and teratogenic effects of anticoagulants on rat embryonic development using in vitro culture method and genotoxicity assay. Anat Histol Embryol. 2006;35(2):84-92.
Uysal, I. I., Karabulut, A. K., Ozdemir, K., Aksoy, M., Altunkeser, B. B., & Acar, H. (2006). Investigation of direct toxic and teratogenic effects of anticoagulants on rat embryonic development using in vitro culture method and genotoxicity assay. Anatomia, Histologia, Embryologia, 35(2), 84-92.
Uysal II, et al. Investigation of Direct Toxic and Teratogenic Effects of Anticoagulants On Rat Embryonic Development Using in Vitro Culture Method and Genotoxicity Assay. Anat Histol Embryol. 2006;35(2):84-92. PubMed PMID: 16542172.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Investigation of direct toxic and teratogenic effects of anticoagulants on rat embryonic development using in vitro culture method and genotoxicity assay. AU - Uysal,I I, AU - Karabulut,A K, AU - Ozdemir,K, AU - Aksoy,M, AU - Altunkeser,B B, AU - Acar,H, PY - 2006/3/18/pubmed PY - 2006/7/4/medline PY - 2006/3/18/entrez SP - 84 EP - 92 JF - Anatomia, histologia, embryologia JO - Anat Histol Embryol VL - 35 IS - 2 N2 - Heparin and low molecular weight heparins (LMWHs) are used to reduce the incidence of venous thromboembolism in pregnancy. Although, these agents have been shown to be safe when used during pregnancy, the studies about direct toxic and teratogenic effects of these drugs on embryonic development are limited. In this study, the effects of heparin and LMWHs on rat embryonic development were investigated by using in vitro embryo culture and micronucleus (MN) assay methods. Rat embryos were cultured in vitro in the presence of different concentrations of heparin (5-40 IU/ml), dalteparin (2.5-20 IU/ml), enoxaparin (25-100 microg/ml) and nadroparin (1-4 IU/ml). Effects of anticoagulants on embryonic developmental parameters were compared and embryos were evaluated for the presence of any malformations. After culturing the embryos, classic MN assay was performed. Anticoagulants significantly decreased all growth and developmental parameters dose-dependently. Dalteparin and enoxaparin were found to cause more developmental toxicity than heparin and nadroparin. Along with haematoma in general, heparin and nadroparin caused maxillary deformity, situs inversus and oedema most frequently, while neural tube defects were observed with dalteparin and enoxaparin. All agents also significantly induced MN formation in rat embryonic blood cells. These results indicate the possible genotoxic effects of anticoagulant agents on the developing rat embryo when applied directly. SN - 0340-2096 UR - https://www.unboundmedicine.com/medline/citation/16542172/Investigation_of_direct_toxic_and_teratogenic_effects_of_anticoagulants_on_rat_embryonic_development_using_in_vitro_culture_method_and_genotoxicity_assay_ L2 - https://doi.org/10.1111/j.1439-0264.2005.00642.x DB - PRIME DP - Unbound Medicine ER -