Serum Adropin Levels in a Preeclampsia Like L-Name Rat Model Treated with Sildenafil Citrate

Abstract
Background: Preeclampsia, a hypertensive disorder of pregnancy, is detrimental to both mother and fetus. Sildenafil been proposed as a potential therapy to reduce blood pressure and improve uteroplacental perfusion in preeclamptic patients. Adropin is a novel secreted energy homeostasis protein regulating carbohydrate, lipid and protein metabolism, maternal adropin levels in Preeclampsia were still controversy.
Aim of the Work: To evaluate serum levels of adropin in preeclampsia-like rat model and in preeclamptic rats treated with Sildenafil and to investigate their associations with some inflammatory, oxidative stress, and metabolic parameters.
Material and Methods: 32 pregnant rats were divided randomly into four groups (n=8): Control group, sildenafil treated group, L-NAME group to induce pre-eclampsia and L-NAME with sildenafil treated group. In all groups, maternal Body Mass Index (BMI), placental weights, fetal weights, maternal mean arterial blood pressure (MAP), total urinary proteins, serum glucose, insulin and calculated Homeostatic Model Assessment of Insulin Resistance index (HOMA-IR), serum urea, creatinine, Triglycerides (TGs), Total Cholesterol (TC), Low Density Lipoproteins-cholesterol (LDL-c), High Density Lipoproteins-cholesterol (HDL-c), C Reactive Protein (CRP), Endothelin-1 (ET-1), and adropin were measured, also placental Malondialdehyde (MDA) levels, and activities of the antioxidant enzymes Superoxide Dismutase (SOD) and glutathione peroxidase (GSH) in placental homogenates were determined plus histopathological examination of placental sections were done.
Results: L-NAME induced preeclampsia in rats and they showed significant increase in MAP, total urinary proteins, serum levels of glucose, insulin, calculated HOMA-IR, serum urea, creatinine, CRP, ET-1, TGs, TC, LDL-c, adropin and placental tissue MDA with significant reduction in maternal BMI, placental weights, fetal weights, serum HDL-c and placental tissue SOD and GSH activities as compared to other groups, additionally, L-NAME treated and L-NAME + SILD treated groups revealed positive significant correlations between adropin levels and MAP, total urinary proteins, serum levels of urea, creatinine, CRP, ET-1, TGs, TC, LDL-c, and placental tissue MDA, however they showed negative corre-lations between adropin and BMI, placental weights, fetal weights, serum HDL-c and placental tissue SOD and GSH activities.
Conclusion: Increased maternal adropin levels in preec-lampsia like model in rats might represent a regulatory feed-back mechanism against endothelial placental dysfunction, insulin resistance, inflammation and oxidative stress which associated with preeclampsia, hence identify it as a potentially protective agent against preeclampsia development. Sildenafil ameliorates preeclampsia symptoms, inflammation and oxi-dative stress in a rat model of preeclampsia.