Investigation of sestrin 2 NRF 2 /KEAP 1 pathway in serum of patients with gestational diabetes mellitus

Sestrin-2, Nuclear Factor Erythroid 2-related Factor 2 (Nrf2), Kelch-like ECH-associated protein-1 (Keap-1),which are oxidati ve stress parameters invol ved in the etiopathogenesis of gestational diabetes mellitus in the sera of patients with Gestational Diabetes Mellitus (GDM) It is aimed to in vestigate the le vels of hypoxia-inducible factor 1α (HIF-1α), Extracellular signal regulated protein kinase (ERK1/2), Superoxide dismutase (Sod), Glutathione peroxidase (GSH-Px) and 4 Hydroxinonenal (4-HNE). In this study, we aimed to determine and compare the le vels of oxidati ve stress parameters in pregnant women with gestational diabetes, healthy pregnant women without chronic diseases and healthy women without chronic diseases, and to in vestigate the potential relationship of oxidati ve stress in the etiology of gestational diabetes and to contribute to the literature in which there is not enough study on this subject. In this study, we aimed to determine and compare the le vels of oxidati ve stress parameters in pregnant women with gestational diabetes, healthy pregnant women without chronic diseases and healthy women without chronic diseases, and to in vestigate the potential relationship of oxidati ve stress in the etiology of gestational diabetes and to contribute to the literature in which there is not enough study on this subject. Demographic parameters including age, gravida, parity, number of abortions, weeks of gestation and body mass index of the patients were recorded. The blood taken from the groups was divided into ependorfs after centrifugation, stored in the-800C deep freezer in the biochemistry department, and then in the serum obtained, Sestrin-2, Nuclear Factor Erythroid 2-related Factor 2 (Nrf2), Kelch-like ECH-associated protein-1 (Keap)-1), Hypoxia-inducible factor 1α (HIF-1α), Extracellular signal regulated protein kinase (ERK1/2), Superoxide dismutase, Glutathione peroxidase and 4-Hydroxynonenal le vels were studied by ELIZA method. Sestrin-2 values were found to be 3.54 ± 1.34, 4.21 ± 1.56, and 4.11 ± 1.14 ng/mL in women in I, II, and III, respecti vely (p=0.035). Nuclear Factor Erythroid 2-related Factor 2 (Nrf2) values were found as (12.74 ± 3.7813.85 ± 5.3712.35 ± 3.09)ng/mL, respecti vely (p=0.891). Kelch-like ECH-associated protein-1 (Keap-1) values were found to be 576.43 ± 166.19627.42 ± 198.47528.65 ± 113.01ng/mL, respecti vely (p=0.246). Hypoxia-inducible factor 1α (HIF-1α) values were found to be 2.85 ± 0.73.3 ± 1.472.52 ± 0.91.ng/mL, respecti vely (p=0.083). Extracellular signal regulated protein kinase (ERK1/2) values were found to be 926.92 ± 198.32968.25 ± 239.2821.31 ± 158.42ng/mL, respecti vely (p=0.026*). Superoxide dismutase values were found as 131.83 ± 24.87,185.79 ± 90.42138.39 ± 26.31U/L, respecti vely (p=0.080). Glutathione peroxidase values were 69.48 ± 19.6679.49 ± 23.8181.72 ± 16.82U/L, respecti vely (p=0.068). 4-Hydroxynonenal values were 22.77 ± 6.0221.13 ± 5.6217.05 ± 3.31 ng/mL, respecti vely (p=0.001*). In demographic parameters, female age was found to be significantly higher in group I compared to groups II and III (p=0.012). There was no difference between groups I and II in terms of obstetric parameters. Body mass index was found to be significantly higher in group I compared to groups II and III (p=0.001). Body mass index was found to be significantly higher in group I compared to groups II and III (p=0.001). Sestrin-2 le vels were found to be significantly lower in group I compared to groups II and III (p=0.028 and 0.023). This difference in Sestrin-2 le vels, which plays a role in oxidati ve stress, indicates the role of oxidati ve stress in gestational diabetes mellitus. Although NRF2 le vels also play a role in oxidati ve stress, no significant difference was found in our study (p=0.891). Although Keap-1 and HIF-1α le vels are also a parameter with a role in oxidati ve stress, no significant difference was found between the groups (p=0.246 and 0.083). Although ERK1/2 le vels were lower in non-pregnant women, no significant difference was found between groups I and II in terms of gestational diabetes (p=0.453). Again, SOD and GSHPx le vels, which play a role in antioxidant balance in oxidati ve stress, were found to be lower in group I compared to group II, but no statistical difference was found (p=0.08 and 0.068). In oxidati ve stress, there was no significant difference in the 4-hydroxy-2-nonenal (4-HNE) le vels of reacti ve carbonyl species deri ved from lipid peroxidation between groups I and II (p=0.567), whereas in group III with non-pregnant women, it was compared to groups I and II. was found to be significantly lower than the ratio (p=0.001 and 0.003). The fact that Sestrin-2 le vels, which ha ve a role in oxidati ve stress, were found to be low in women with gestational diabetes mellitus in our study is interesting, and further studies are needed in terms of its role in this pathway and its use in identifying risky women. Keywords:Pregnancy, Gestational Diabetes Mellitus, Oxidati ve stress, Sestrin-2