Effect of Maternal Diabetes on Pre- and Post-Natal Redox Status of F1 Rat Offspring
Effect of Maternal Diabetes on Pre- and Post-Natal Redox Status of F1 Rat Offspring作者机构：Department of Biochemistry Medical Research Institute University of Alexandria Alexandria Egypt
出 版 物：《Open Journal of Endocrine and Metabolic Diseases》 (内分泌与新陈代谢疾病期刊（英文）)
年 卷 期：2014年第4卷第5期
页 面：111-127页
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
主 题：Fetal Origin of Disease Diabetes GSH Redox 8-Oxo-dG Apoptosis Oxidative Stress
摘 要：Background: The oxidative stress and disturbed redox signaling during gestation my play an important role in the fetal programming of adult diabetes. Objective: The study aimed to investigate the effects of maternal diabetes on pre- and post-natal pancreatic and peripheral tissues redox and oxidative status in order to clarify their role in the diabetogenic programming of F1 offspring. Methods: Two groups of female Wistar rats were used (diabetic and control);diabetes was neonatally induced by STZ injection to 5-day old rats. 10 pregnancies of each group were terminated at GD 17 to obtain placentas and fetal pancreas, liver, muscle and adipose tissues for prenatal measurements. The rest of pregnancies were completed to term and the offspring were weaned to control diet or high-caloric (HCD) diet and followed up for 30 weeks. Every 5 weeks 10 male rats were sacrificed and serum and tissues were obtained for assessment of fasting blood glucose, tissues content of 8-oxo-dG, TBARS, GSH, GSSG, antioxidant enzymes and caspase-3. Results: The results indicated that, prenatally redox status of the foetuses of diabetic mothers is shifted toward more oxidizing environment which results from elevated oxidative stress and impaired antioxidants as indicated by elevated fetal tissues content of 8-oxo-dG, TBARS and GSSG and decreased GSH and GSH/GSSG ratio. All of these induce the apoptotic pathway in fetal pancreas. Postnatally, impaired glucose tolerance in the offspring of diabetic mothers is detected at 15th week of age and no hyperglycemia was detected until age of 30 weeks in the offspring under CD while some of offspring under HCD at age 25 weeks and most of them at 30 weeks have developed hyperglycemia. The pancreas of the offspring of diabetic mothers suffers from oxidative stress from the 5th week of age as indicated by elevated levels of nuclear and mitochondrial 8-oxo-dG contents and TBARS. Also, GSH level showed depletion with age and the activity of glutathione reduc
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