Skip to main content
SpringerLink
Log in

Teratogenic effects of diabetes mellitus in the rat. Prevention by vitamin E

  • Originals
  • Published:
Diabetologia Aims and scope Submit manuscript

Summary

We wanted to determine whether administration of vitamin E could reduce the production of free radicals which could play a role in the teratogenic effects of diabetes mellitus. Diabetes was induced in Wistar rats by the intravenous administration of streptozotocin. The animals were divided into six groups: one with no supplement (D) and two, supplemented during pregnancy either with oral vitamin E (150 mg/day) (D + E) or with a placebo (safflower oil) (D + O). Three other groups were kept under the same conditions, but were treated with insulin: D + I, D + I + E and D + I + O. There were three groups of matched controls: C, C + E and C + O. All animals were killed on day 11.5 of pregnancy. In C animals the percentages of reabsorptions and malformations were 1.3 and 2%, respectively, comapred with 23.6, 24.3, 6.2 and 13.2%, respectively in D and D + I groups. The crown-rump length, number of somites, and protein and DNA content were higher in C animals than in the diabetic rats, independent of insulin treatment. When vitamin E was administered no changes in these parameters were observed in C and D + I animals; however, in the D mothers it reduced the rate of embryo malformations to 4.6% and increased the crown-rump length and the number of somites. However, vitamin E did not modify the protein and DNA content and the percentage of reabsorptions. In conclusion, administration of vitamin E to diabetic animals decreases the rate of embryo malformations and increases their size and maturation, supporting a role for free radicals in the teratogenic effects of diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Lucas MJ, Leveno KJ, Williams ML, Raskin P, Whalley PJ (1989) Early pregnancy glycosylated hemoglobin, severity of diabetes, and fetal malformations. Am J Obstet Gynecol 161: 426–431

    Google Scholar 

  2. Mills JL, Knopp RH, Simpson JL et al. (1988) Lack of relation of increased malformation rates in infants of diabetic mothers to glycemic control during organogenesis. N Engl J Med 318: 671–676

    Google Scholar 

  3. Miller E, Hare JW, Cloherty JP et al. (1981) Elevated maternal hemoglobin a in early pregnancy and major congenital anomalies in infants of diabetic mothers. N Engl J Med 304: 1331–1334

    Google Scholar 

  4. Mills JL, Simpson JL, Driscoll SG et al. (1988) Incidence of spontaneous abortion among normal women and insulin-dependent diabetic women whose pregnancies were identified within 21 days of conception. N Engl J Med 319: 1617–1622

    Google Scholar 

  5. Freinkel N (1980) Banting lecture 1980. Of pregnancy and progeny. Diabetes 29: 1023–1035

    Google Scholar 

  6. Eriksson UJ, Borg LAH, Forsberg H, Styrud J (1991) Diabetic embryopathy. Studies with animal and in vitro models. Diabetes 40: 94–97

    Google Scholar 

  7. Freinkel N (1988) Diabetic embryopathy and fuel-mediated organ teratogenesis: lessons from animal models. Horm Metab Res 20: 463–475

    Google Scholar 

  8. Eriksson RSM, Thunberg L, Eriksson UJ (1989) Effects of interrupted insulin treatment on fetal outcome of pregnant diabetic rats. Diabetes 38: 764–772

    Google Scholar 

  9. Horton WE, Sadler TW (1983) Effects of maternal diabetes on early embryogenesis. Alterations in morphogenesis produced by the ketone body, B-hydroxybutyrate. Diabetes 32: 610–616

    Google Scholar 

  10. Buchanan TA, Denno KM, Sipos GF, Sadler TW (1994) Diabetic teratogenesis: in vitro evidence for a multifactorial etiology with little contribution from glucose per se. Diabetes 43: 656–660

    Google Scholar 

  11. Eriksson UJ, Karlsson M, Styrud J (1987) Mechanisms of congenital malformations in diabetic pregnancy. Biol Neonate 51: 113–118

    Google Scholar 

  12. Eriksson UJ, Borg LAH (1991) Protection by free oxygen radical scavenging enzymes against glucose-induced embryonic malformations in vitro. Diabetologia 34: 325–331

    Google Scholar 

  13. Eriksson UJ, Borg LAH, Forsberg H, Simán MC, Suzuki N, Yang X (1995) Advances in the understanding of diabetic embryopathy: antioxidant mechanisms. 2nd Inter Symp Diabetes and Pregnancy in the 90's. Jerusalem, Israel (Abstract)

  14. Jain SK, Levine SN, Duett J, Hollier B (1990) Elevated lipid peroxidation levels in red blood cells of streptozotocin-treated diabetic rats. Metabolism 39: 971–975

    Google Scholar 

  15. Morel DW, Chisolm GM (1989) Antioxidant treatment of diabetic rats inhibits lipoprotein oxidation and cytotoxicity. J Lipid Res 30: 1827–1834

    Google Scholar 

  16. Bonet B, Knopp RH (1992) Accelerated LDL oxidation in diabetic gestation. 2nd Internat Graz Symp on Gestational Diabetes (Abstract)

  17. Mullarkey CJ, Edelstein D, Brownlee M (1990) Free radical generation by early glycation products: a mechanism for accelerated atherogenesis in diabetes. Biochem Biophys Res Commun 173: 932–939

    Google Scholar 

  18. Hunt JV, Smith CCT, Wolff SP (1990) Autooxidative glycosylation and possible involvement of peroxides and free radicals in LDL modification by glucose. Diabetes 39: 1420–1424

    Google Scholar 

  19. Jain SK, Levine SN, Duett J, Hollier B (1991) Reduced vitamin E and increased lipofuscin products in erythrocytes of diabetic rats. Diabetes 40: 1241–1244

    Google Scholar 

  20. Cunningham JJ, Ellis SL, McVeigh KL, Levine RE, Calles-Escandon J (1991) Reduced mononuclear leukocyte ascorbic acid content in adults with insulin-dependent diabetes mellitus consuming adequate dietary vitamin C. Metabolism 40: 146–149

    Google Scholar 

  21. Tsai EC, Hirsch IB, Brunzell JD, Chait A (1994) Reduced plasma peroxyl radical trapping capacity and increased susceptibility of LDL to oxidation in poorly controlled IDDM. Diabetes 43: 1010–1014

    Google Scholar 

  22. Martín A, Herrera E (1991) Different responses to maternal diabetes during the first and second half of gestation in the streptozotocin-treated rat. Isr J Med Sci 27: 442–448

    Google Scholar 

  23. Martín A, Ramos P, Herrera E (1993) Modulation of lipoprotein lipase activity in adipose tissue during late pregnancy. In: Medina JM, Quero J (eds) Physiologic basis of perinatal care. Ediciones Ergon, Madrid, pp 117–122

    Google Scholar 

  24. Lowry OH, Rosebrough NJ, Farr AL et al. (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275

    Google Scholar 

  25. Hinegardner RT (1971) An improved fluorometric assay for DNA. Anal Biochemistry 39: 107–201

    Google Scholar 

  26. Somogyi M (1945) Determination of blood sugar. J Biol Chem 160: 69–73

    Google Scholar 

  27. Bonet B, Herrera E (1991) Maternal hypothyroidism during the first half of gestation compromises normal catabolic adaptations of late gestation in the rat. Endocrinology 129: 210–216

    Google Scholar 

  28. Williamson DH, Mellanby T, Krebs HA (1962) A enzymatic determination of D-Β-hydroxybutiric acid and acetonic acid in blood. Biochem J 82: 90–96

    Google Scholar 

  29. Otani H, Tanaka O, Tatewaki R, Naora H, Yoneyama T (1991) Diabetic environment and genetic predisposition as causes of congenital malformations in NOD mouse embryos. Diabetes 40: 1245–1250

    Google Scholar 

  30. Pampfer S, Wuu YD, Vanderheyden I, De Hertogh R (1994) In vitro study of the carry-over effect associated with early diabetic embryopathy in the rat. Diabetologia 37: 855–862

    Google Scholar 

  31. Diamond MP, Harbert-Moley K, Logan J et al. (1990) Manifestation of diabetes mellitus on mouse follicular and preembryo development: effect of hyperglycemia per se. Metabolism 39: 220–224

    Google Scholar 

  32. Tanigawa K, Kawaguchi M, Tanaka O, Kato Y (1991) Skeletal malformations in rat offspring. Long-term effect of maternal insulin-induced hypoglycemia during organogenesis. Diabetes 40: 1115–1121

    Google Scholar 

  33. Buchanan TA, Schemmer JK, Freinkel N (1986) Embryotoxic effects of brief maternal insulin-hypoglycemia during organogenesis in the rat. J Clin Invest 78: 643–649

    Google Scholar 

  34. Esterbauer H, Gebicki J, Puhl H, Jürgens G (1992) The role of lipid peroxidation and antioxidants in oxidative modification of LDL. Free Rad Biol Med 13: 341–390

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Sectión de Endocrinología, Hospital del Niño JesÚs, Madrid, Spain

    M. Viana & B. Bonet

  2. Centro de Ciencias Experimentales y Técnicas, Universidad de San Pablo, CEU, P.O. Box 67, E-28660, Boadilla del Monte (Madrid), Spain

    M. Viana, E. Herrera & B. Bonet

Authors
  1. M. Viana
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Herrera
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. Bonet
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Viana, M., Herrera, E. & Bonet, B. Teratogenic effects of diabetes mellitus in the rat. Prevention by vitamin E. Diabetologia 39, 1041–1046 (1996). https://doi.org/10.1007/BF00400652

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00400652

Keywords

Search

Navigation