High sucrose low copper diet in pregnant diabetic rats induces transient oxidative stress, hypoxia, and apoptosis in the offspring's liver

Zivanit Ergaz, Liza Weinstein-Fudim, Asher Ornoy

פרסום מחקרי: פרסום בכתב עתמאמרביקורת עמיתים

1 ציטוט ‏(Scopus)

תקציר

Background: Hyperglycemia-related oxidative stress and hypoxia are important mechanisms responsible for diabetes-induced embryopathy and other complications. High sucrose low copper diet (HSD), but not regular diet (RD), induces type 2 diabetes in the inbred Cohen diabetic sensitive (CDs) rats but not in the Sabra control rats. We recently demonstrated long-term changes of DNA methylation and gene expression in various groups of genes, including genes involved in oxidant-antioxidant activity in the liver of 2–4-week-old CDs offspring of diabetic dams. We now studied the postnatal effects of diabetes and/or HSD on several liver metabolic parameters in these offspring. Methods: we studied lipid peroxidation, activity of the antioxidants enzymes superoxide dismutase (SOD) and Catalase (CAT). By immunohistochemistry: protein oxidation by nitrotyrosine staining, hypoxia inducing factor1α (HIF1α), apoptosis [caspase 3, bcl-2-like protein (BAX)], proliferation [proliferating cell nuclear antigen (PCNA)] and NF-κB. Results: In the Sabra rats fed HSD only few, early and transitional changes were observed in lipid peroxidation, SOD and CAT activity. In the CDs fed HSD more significant changes in lipid and protein oxidation, HIF1α, apoptosis and proliferation were observed, persisting for longer. Conclusions: The changes in the Sabra rats HSD were attributed to the pro-oxidant effects of the diet and those in the diabetic CDs to the HSD and maternal diabetes. In light of the DNA methylation changes in the liver of the CDs HSD, we presume that changes in gene expression are responsible for our findings, and that similar changes may lead to the metabolic syndrome at adulthood.

שפה מקוריתאנגלית
עמודים (מ-עד)1001-1015
מספר עמודים15
כתב עתBirth Defects Research
כרך110
מספר גיליון12
מזהי עצם דיגיטלי (DOIs)
סטטוס פרסוםפורסם - 17 יולי 2018
פורסם באופן חיצוניכן

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