Initiation of phenytoin teratogenesis: Pharmacologically induced embryonic bradycardia and arrhythmia resulting in hypoxia and possible free radical damage at reoxygenation

Teratology

Volumn 56, Issue 4, 1997, Pages 271-281

  Danielsson, B R ^a,b   Azarbayjani, F ^a   Skold A C ^a,b   Webster, W S ^c  

^a UPPSALA UNIVERSITY   (Sweden)

^b Safety Assessment   (Sweden)

^c UNIVERSITY OF SYDNEY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

FREE RADICAL; PHENYTOIN;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BRADYCARDIA; CARDIOTOXICITY; CONTROLLED STUDY; EMBRYO; EMBRYO CULTURE; HEART ARREST; HEART ARRHYTHMIA; HEART RATE; HYPOXIA; MOUSE; NONHUMAN; PRIORITY JOURNAL; RAT; REOXYGENATION; TERATOGENESIS;

ANIMALS; ANOXIA; ANTI-ARRHYTHMIA AGENTS; ARRHYTHMIA; BRADYCARDIA; CELL CULTURE TECHNIQUES; DOSE-RESPONSE RELATIONSHIP, DRUG; EMBRYO; FEMALE; FREE RADICALS; HEART; HEART RATE; MICE; MICE, INBRED A; MICE, INBRED C57BL; OXYGEN; PHENYTOIN; PREGNANCY; RATS; RATS, SPRAGUE-DAWLEY;

ANIMALIA;

EID: 0031444561     PISSN: 00403709     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1096-9926(199710)56:4<271::AID-TERA6>3.0.CO;2-1     Document Type: Article

References (57)

1. Abrahamsson, C., M. Palmer, B. Ljung, G. Duker, C. Baarnhielm, L. Carlsson, and B. Danielsson (1994) Induction of rhythm abnormalities in the fetal rat heart. A tentative mechanism for the embryotoxic effect of class III antiarrhythmic agent almokalant. Cardiovasc. Res., 28:337-344.
2. Ban, Y., R. Konishi, K. Kawana, T. Nakatsuka, and T. Fujii (1992) Embryonic effects of class III antiarrhythmic agent, L-691, 121 in rats. Teratology, 45:462.
3. Barber, C.V., M.B. Carda, and A.G. Fantel (1993) A new technique for culturing rat embryos in vitro between gestation day 14 and 15. Toxicol In Vitro. 7:695-700.
4. Bigger, J.T., and B.F. Hoffman (1980) Antiarrhythmic drugs. In: The Pharmacological Basis of Therapeutics, 6th ed. A.G. Gilman, L.S. Goodman, and A. Gilman, eds. MacMillan Publishing Co., New York, pp. 761-792.
5. Brent, R.L., and J.B. Franklin (1960) Uterine vascular clamping: New procedures for the study of congenital malformations. Science, 132:89-91.
6. Chernhoff, N., and C.T. Grabowski (1971) Responses of the rat foetus to maternal injections of adrenaline and vasopressin. Br. J. Pharmacol., 43:270-278.
7. Danielson, M.K., B.R.G. Danielsson, H. Marchner, M. Lundin, E. Rundqvist, and S. Reiland (1992) Histopathological and hemodynamic studies supporting hypoxia and vascular disruption as explanation to phenytoin teratogenicity. Teratology, 46:485-497.
8. Danielsson, B.R. (1993) Malformations and fetal hypoxia induced by exaggerated pharmacological effects. In: Developmental Toxicology: Preclinical and Clinical Data in Retrospect. Sundvall, A., B.R. Danielsson, O. Hagberg, E. Lindgren, P. Sjöberg, A. Victor, eds. Tryckgruppen, Stockholm, pp. 44-57.
9. Danielsson, B.R., and W.S. Webster (1996) Cardiovascular active drugs. In: Development Drug Toxicity in Embryonic Development. Handbook of Experimental Pharmacology. R.J. Kavlock and G. Daston, eds. Springer-Verlag, New York, pp. 161-190.
10. Danielsson, B.R.G., S. Reiland, E. Rundqvist, and M. Danielson (1989) Digital defects induced by vaso-dilating agents. Relationship to reduction in utero-placental blood flow. Teratology, 40:351-357.
11. Danielsson, B.R.G., S. Reiland, E. Rundqvist, M. Danielson, L. Dencker, and C-G. Regård (1990) Histological and in vitro studies supporting decreased utero-placental blood flow as explanation to digital defects after administration of vasodilators. Teratology, 41:185-193.
12. Danielsson, B.R.G., K. Danielson, and S. Reiland (1991) Distal limb defects caused by phenytoin: Relation to vascular disruption and hypoxia. Teratology, 44:26A.
13. Danielsson, B.R.G., M. Danielson, E. Rundqvist, and S. Reiland (1992) Identical phalangeal defects induced by phenytoin and nifedipine suggest fetal hypoxia and vascular disruption behind phenytoin teratogenicity. Teratology, 45:247-258.
14. Danielsson, B.R.G., K. Danielson, and T. Tomson (1995) Phenytoin causes phalangeal hypoplasia in the rabbit fetus at clinically relevant concentrations. Teratology, 52:252-259.
15. Dansky, V.L., and R.H. Finnell (1991) Parental epilepsy, anticonvulsant drugs, and reproductive outcome: Epidemiologic and experimental findings spanning three decades; 2: human studies. Reprod. Toxicol., 5:301-335.
16. De Moraes, S., J.C. Carvalho, R.S. Mathias, and M.T. Cavalacante (1995) Relative hypoxia-induced contraction of the isolated human umbilical artery. Pharmacol. Toxicol., 76:218-20.
17. Ducsay, C.A., J.S. Thompson, A.T. Wu, and M.J. Novy (1987) Effects of calcium entry blocker (nicardipine) tocolysis in rhesus macaques: Fetal plasma concentrations and cardiorespiratory changes. Am. J. Obstet. Gynecol. 157:1482-6.
18. Fantel, A.G., C.V. Barber, and B. MacKler (1992) Ischemia/reperfusion: A new hypothesis for the developmental toxicity of cocaine. Teratology, 46:285-292.
19. Fantel, A.G., R.E. Person, R.W. Tumbic, T.D. Nguyen, and B. MacKler (1995) Studies of mitochondria in oxidative embryotoxicity. Teratology, 52:190-195.
20. Finnell, H.R., and L.V. Dansky (1991) Parental epilepsy, anticonvulsant drugs, and reproductive outcome: Epidemiologic and experimental findings spanning three decades; 1: animal studies. Reprod. toxicol., 5:281-299.
21. Finnell, R.H., and J.H. DiLiberti (1983) Hydantoin induced teratogenesis: Are some oxide intermediates really responsible? Helv. Paediatr. Acta., 38:171-177.
22. Franklin, J.B., and R.L. Brent (1964) The effect of uterine vascular clamping on the development of rat embryos three to fourteen days old. J. Morphol., 115:273-290.
23. Gaily, E. (1990) Distal phalangeal hypoplasia in children with prenatal phenytoin exposure. Am. J. Med. Genet., 35:403-414.
24. Gutteridge, J.M.C. (1993) Free radicals in disease processes. A compilation of cause and consequence. Free Rad. Comm., 19:141-158.
25. Hansen, D.K., and M.E. Hodes (1983a) Comparative teratogenicity of phenytoin among several inbred strains of mice. Teratology, 28: 175-9.
26. Hansen, D.K., and M.E. Hodes (1983b) Metabolism of phenytoin in teratogenesis-susceptible and -resistant strains of mice. Drug Metab. Disp., 11:21-4.
27. Hanson, J.W. (1986) Teratogen update: Fetal hydantoin effects. Teratology, 33:349-353.
28. Harake, B., R.D. Gilbert, S. Ashwad, and G.G. Power (1987) Nifedipine: Effects on fetal and maternal hemodynamics in pregnant sheep. Am. J. Obstet. Gynecol., 157:1003-1008.
29. Harbison, R.D., and B.A. Becker (1972) Dephenylhydantoin teratogenicity in rats. Toxicol. Appl. Pharmacol. 22:193-200.
30. Harbison, R.D., J.S. MacDonald, B.J. Sweetman, and D. Taber (1977) Proposed mechanism for diphenylhydantoin-induced teratogenesis. Pharmacologist, 19:179.
31. Howe, A.M., A.H. Lipson, L.J. Sheffield, E.A. Haan, J.L. Halliday, F. Jenson, D.J. David, and W.S. Webster (1995) Prenatal exposure to phenytoin, facial development, and a possible role for vitamin K. Am. J. Med. Genet., 58:238-244.
32. Leist, K.H., and J. Grauwiler (1974) Fetal pathology in rats following uterine vessel clamping on day 14 of gestation. Teratology, 10:55-68.
33. Lindhout, D. (1993) Antiepileptic drugs: Clinical results and mechanisms. In: Workshop on Developmental Toxicology Preclinical and Clinical Data in Retrospect. A. Sundwall, B.R. Danielsson, O. Hagberg, E. Lindgren, P. Sjöberg, and A. Victor, eds. Tryckgruppen, Stockholm, pp. 111-121.
34. Lirette, M., R.H. Holbrook, and M. Katz (1987) Cardiovascular and uterine blood flow changes during nicardipine Hcl tocolysis in the rabbit. Obstet. Gynecol., 69:79-82.
35. Lundgren, Y., P. Thalen, and M. Nordlander (1992) Effects of felodipine on uteroplacental blood flow in normotensive rabbits. Pharmacol. Toxicol. 71:361-364.
36. Martz, F., C. III. Failinger, and D.A. Blake (1977) Phenytoin teratogenesis: Correlation between embryopathic effect and covalent binding of putative arene oxide metabolite in gestational tissue. J. Pharmacol. Exp. Ther., 203:231-9.
37. McCord, J.M. (1993) Human disease, free radicals and the oxidant/ antioxidant balance. Clin. Biochem., 26:261-274.
38. Mercier-Parot, I., and H. Tuchmann-Duplessis (1974) The dysmophogenic potential of phenytoin: Experimental observations. Drugs, 8:340-53.
39. Millicovsky, G., and M.C. Johnston (1981) Maternal hyperoxia greatly reduces the incidence of phenytoin-induced cleft lip and palate in A/3 mice. Science, 212:611-72.
40. Monie, I.W., R.M. Armstrong, and M.M. Nelson (1961) Hydrocephalus and other abnormalities in rat young resulting from maternal pteroylglutamic acid deficiency from the 8th to 10th days of pregnancy. Teratology, 1:8.
41. New, D.A.T. (1978) Whole-embryo culture and the study of mammalian embryos during organogenesis. Biol. Rev., 53:81-122.
42. Roberts, L.G., J.B. Laborde, and W. Slikker, JR (1991) Phenytoin teratogenicity and midgestational pharmakokinetics in mice. Teratology, 44:497-505.
43. Skilman, C.A., M.A. Plessinger, J.R. Woods, and K.E. Clark (1985) Effects of graded reductions in uteroplacental blood flow in the fetal limp. Am. J. Physiol., 249:H1098-H1105.
44. Spence, G.S., C. Vetter, and C-M Hoe (1994) Effects of the class III antiarrhythmic, dofetilide (UK-68,798) on the heart rate of midgestation rat embryos in vitro. Teratology, 49:282-292.
45. Spinato, J.A., B.M. Sibai, and G.D. Anderson (1986) Fetal distress after hydralazine therapy for severe pregnancy-induced hypertension. South. Med. J., 79:559-562.
46. Sullivan, F.M., and P.R. McElhatton (1977) A comparison of the teratogenic activity of the antiepileptic drugs carbamazepine, clonazepam, ethosuximide, phenobarbital, phenytoin, and primidone in mice. Toxicol. Appl. Pharmacol., 40:365-78.
47. Watkinson, W.P., and G. Millicovsky (1983) Effect of phenytoin on maternal heart rate in A/J mice: Possible role in teratogenesis. Teratology, 28:1-8.
48. Webster, W.S., and P.D.C. Brown-Woodman (1990) Cocaine as a cause of congenital malformations of vascular origin: Experimental evidence in the rat. Teratology, 41:689-697.
49. Webster, W.S., A.H. Lipson, and P.D.C. Brown-Woodman (1987) Uterine trauma and limb defects. Teratology, 35:253-260.
50. Webster, W.S., P.D.C. Brown-Woodman, A.H. Lipson, and H.E. Ritchie (1991) Fetal brain damage in the rat following prenatal exposure to cocaine. Neurotoxicol. Teratol., 13:621-626.
51. Webster, W.S., P.D.C. Brown-Woodman, M. Snow, and B.R.G. Danielsson (1996) Teratogenic potential of almokalant, dofetilide, and d-sotalol: Drugs with potassium channel blocking activity. Teratology, 53:168-175.
52. Wells, P.G., and H.P.N. Vo (1989) Effects of the tumor promoter 12-0-tetradecanolylphorbol-13-acetate on phenytoin-induced embryopathy in mice. Toxicol. Appl. Pharmacol., 97:398-405.
53. Wilson, J.G., and R. Fradkin (1967) Interrelations of mortality and malformations in rats. Teratology, 7:57-8.
54. Winer, B.J., D.R. Brown, and K.M. Michels (1991) Statistical Principles in Experimental Design, 3rd ed. New York: McGraw-Hill.
55. Winn, M., and P.G. Wells (1995) Phenytoin-initiated DNA oxidation in murine embryo culture, and embryo protection by the antioxidative enzymes superoxide dismutase and catalase: Evidence for reactive oxygen species-mediated DNA oxidation in the molecular mechanism of phenytoin teratogenicity. Mol. Pharmacol., 48:112-120.
56. Yaari, Y., M.E. Selzor, and J.H. Pineus (1986) Phenytoin: Mechanisms of its anticonvulsant action. Ann. Neurol., 20:171-184.
57. Yu, W.K., and P.G. Wells (1995) Evidence for lipoxygenase-catalyzed bioactivation of phenytoin to a teratogenic reactive intermediate: In vitro studies using linoleic acid-dependent soybean lipoxygenase, and in vivo studies using pregnant CD-1 mice. Toxicol. Appl. Pharmacol., 131:1-12.