Relation of Circulatory Levels of Endothelin-1, Antioxidants, and Inflammatory Markers with Varying Blood Pressure Levels in Preeclampsia: A Case-control Study

Introduction: Preeclampsia is a pregnancy disorder with gestational hypertension and proteinuria, it affects maternalfoetal vasculature. The risk of preeclampsia increases upon exposure to different genetic mutations, environmental changes, obesity, gestational diabetes mellitus, multifoetal gestations, and hydatidiform mole. Preeclampsia affects the mother and foetus; its pathogenesis is complex involving inflammation, stress, and molecular factors. Aim: To measure the circulatory levels of Endothelin-1 (ET-1), Glutathione (GSH), Interleukin-6 (IL-6), and Tumor Necrosis Factor-a (TNF-a) by Enzyme Linked Immunosorbent Assay (ELISA) kit (sandwich) in preeclamptic women and healthy controls. Materials and Methods: The present study was a casecontrol study carried out in the Department of Biochemistry at Government Institute of Medical Science (GIMS), Greater Noida, and Santosh Medical College, Ghaziabad, Uttar Pradesh, India, from November 2018 to November 2020. The demographic data was recorded, and blood samples were studied. Preeclamptic women (cases, n=90) were grouped as group A: with BP 140/90- 149/99 mmHg, group B: with BP 150/100-159/109 mmHg, and group C: with BP 160/110 mmHg along with controls (n=70). The normotensive pregnant women without family history of preeclampsia were included as controls. The competitive ELISA principles were used to quantify ET-1, GSH, IL-6, and TNF-a levels. One-way Analysis of Variance tests (ANOVA) and Tukey Posthoc Test was carried out to compare the clinical characteristics, ET-1, GSH, IL-6, and TNF-a between the cases and controls. Results: The demographic data of age, gestational age, and Body Mass Index (BMI) were not significantly different between cases and control. The ET-1 levels were significantly (p-value=0.042) higher in groups (A: 116±79.4, B: 99.2±72, C: 159±96) than controls (54±49). In contrast, GSH levels were low in preeclampsia. In addition, cases had elevated IL-6 and TNF-a levels (IL-6; groups A: 112.3±49.3, B: 127±17.5, C: 324±52.9, and control 40.3±13, TNF-a; groups A: 241±179, B: 200.9±196, C: 391±299 and controls: 167±104). GSH levels decreased with the rise in Blood Pressure (BP), while IL-6 increased significantly with an increase in BP. Conclusion: Every 10 mmHg increase in BP led to increasing in IL-6 levels. The ET-1 and TNF-alpha levels were increased in all three groups when compared to controls. Similarly, the GSH levels were decreased. Thus, the present study provided evidence that links oxidative stress, inflammation, and a potent vasoconstrictor ET-1 with altered antioxidants (GSH) that led to the pathophysiology of preeclampsia.