Zaken V, Kohen R, Ornoy A
Department of Anatomy and Cell Biology, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
Teratology. 2001 Jul;64(1):33-44. doi: 10.1002/tera.1045.
Diabetes teratogenicity seems to be related to embryonic oxidative stress and the extent of the embryonic damage can apparently be reduced by antioxidants. We have studied the mechanism by which antioxidants, such as vitamins C and E, reduce diabetes-induced embryonic damage. We therefore compared the antioxidant capacity of 10.5-day-old rat embryos and their yolk sacs cultured for 28h in diabetic culture medium with or without vitamins C and E.
The embryos were cultured in 90% rat serum to which 2mg/ml glucose, 2mg/ml beta hydroxy butyrate (BHOB) and 10 microg/ml of acetoacetate were added. Rat embryos were also cultured in a diabetic medium with 25 microg/ml of vitamin E and 50 microg/ml of vitamin C. Control embryos were cultured in normal rat serum with or without vitamins C and E.
Decreased activity of Cu/Zn superoxide dismutase (SOD) and of catalase (CAT) in the "diabetic" embryos and their yolk sacs, and reduced concentrations of low molecular weight antioxidant (LMWA) were found. Under these conditions we also found a decrease in vitamin C and vitamin E concentrations in the embryos, as measured by HPLC. In situ hybridization for SOD mRNA showed a marked reduction of SOD mRNA in the brain, spinal cord, heart and liver of embryos cultured in diabetic medium in comparison to controls. Following the addition of vitamins C and E to the diabetic culture medium, SOD and CAT activity, the concentrations of LMWA, the levels of vitamin C and E and the expression of SOD mRNA in the embryos and yolk sacs returned to normal.
Diabetic metabolic factors seem to have a direct effect on embryonic SOD gene and perhaps genes of other antioxidant enzymes, reducing embryonic endogenous antioxidant defense mechanism. This in turn may cause a depletion of the LMWA, such as vitamins C and E. The addition of these vitamins normalizes the embryonic antioxidant defense mechanism, reducing the damage caused by the diabetic environment.
糖尿病致畸性似乎与胚胎氧化应激有关，而抗氧化剂显然可以减轻胚胎损伤的程度。我们研究了抗氧化剂（如维生素C和维生素E）减轻糖尿病诱导的胚胎损伤的机制。因此，我们比较了在含或不含维生素C和E的糖尿病培养基中培养28小时的10.5日龄大鼠胚胎及其卵黄囊的抗氧化能力。
胚胎在添加了2mg/ml葡萄糖、2mg/mlβ-羟基丁酸（BHOB）和10μg/ml乙酰乙酸的90%大鼠血清中培养。大鼠胚胎也在添加了25μg/ml维生素E和50μg/ml维生素C的糖尿病培养基中培养。对照胚胎在含或不含维生素C和E的正常大鼠血清中培养。
在“糖尿病”胚胎及其卵黄囊中发现铜/锌超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性降低，低分子量抗氧化剂（LMWA）浓度降低。在这些条件下，通过高效液相色谱法测定，我们还发现胚胎中维生素C和维生素E浓度降低。与对照组相比，糖尿病培养基中培养的胚胎脑、脊髓、心脏和肝脏中SOD mRNA的原位杂交显示SOD mRNA明显减少。在糖尿病培养基中添加维生素C和E后，胚胎和卵黄囊中SOD和CAT活性、LMWA浓度、维生素C和E水平以及SOD mRNA表达恢复正常。
糖尿病代谢因子似乎对胚胎SOD基因以及其他抗氧化酶的基因有直接影响，从而降低胚胎内源性抗氧化防御机制。这反过来可能导致LMWA（如维生素C和E）的消耗。添加这些维生素可使胚胎抗氧化防御机制正常化，减少糖尿病环境造成的损伤。
