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.
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References
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
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
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
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
Freinkel N (1980) Banting lecture 1980. Of pregnancy and progeny. Diabetes 29: 1023–1035
Eriksson UJ, Borg LAH, Forsberg H, Styrud J (1991) Diabetic embryopathy. Studies with animal and in vitro models. Diabetes 40: 94–97
Freinkel N (1988) Diabetic embryopathy and fuel-mediated organ teratogenesis: lessons from animal models. Horm Metab Res 20: 463–475
Eriksson RSM, Thunberg L, Eriksson UJ (1989) Effects of interrupted insulin treatment on fetal outcome of pregnant diabetic rats. Diabetes 38: 764–772
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
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
Eriksson UJ, Karlsson M, Styrud J (1987) Mechanisms of congenital malformations in diabetic pregnancy. Biol Neonate 51: 113–118
Eriksson UJ, Borg LAH (1991) Protection by free oxygen radical scavenging enzymes against glucose-induced embryonic malformations in vitro. Diabetologia 34: 325–331
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)
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
Morel DW, Chisolm GM (1989) Antioxidant treatment of diabetic rats inhibits lipoprotein oxidation and cytotoxicity. J Lipid Res 30: 1827–1834
Bonet B, Knopp RH (1992) Accelerated LDL oxidation in diabetic gestation. 2nd Internat Graz Symp on Gestational Diabetes (Abstract)
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
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
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
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
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
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
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
Lowry OH, Rosebrough NJ, Farr AL et al. (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275
Hinegardner RT (1971) An improved fluorometric assay for DNA. Anal Biochemistry 39: 107–201
Somogyi M (1945) Determination of blood sugar. J Biol Chem 160: 69–73
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
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
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
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
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
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
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
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
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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
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DOI: https://doi.org/10.1007/BF00400652