Pre-eclampsia (PE) accompanying acute liver and kidney injury has remained a master cause of both fetal and maternal mortality and morbidity. Vasoactive mediators, oxidative stress and inflammatory imbalanceshave an important role in PE pathogenesis. Apelin is an adipokine that improves endothelial dysfunction; has anti-inflammatory and antioxidant effects; moreover, its level reduced during PE. This study aimed to explore the effects of apelin-13 administration on preeclampsia-associated renal dysfunction and proteinuria. Thirty-three pregnant female rats were divided into three groups; group: 1 (normal pregnant rats), group: 2 (preeclamptic rats); where rats were injected subcutaneously with 75 mg L-NAME/ kg body weight/day beginning from 9th to 20th day of pregnancy andgroup 3 (apelin-13 treated preeclamptic rats); In which L-NAME-induced preeclamptic rats were subcutaneously injected with 6 × 10−8 mol apelin-13/kg body weight/twice daily starting from 6th to 20th day of pregnancy. In all groups, mean arterial blood pressure, total urine protein, serum urea, creatinine, nitric oxide (NO), endothelin-1 (ET-1), interleukin–6 (IL-6) and malondialdhyde (MDA) were measured. Histopathological examination of kidney tissues was also done. preeclamptic rats showed significantly increased mean arterial blood pressure, total urine proteins, serum urea, creatinine, ET-1, IL-6, and MDA, but revealed a significantly decreased serum NO level. On the other hand, apelin treatment significantly improved these parameters together with amelioration of kidney histoarchitecture in the treated group. In conclusion, apelin may be a potentially curative candidate for prohibiting kidney damage and have a therapeutic benefit in PE rat models.

Preeclampsia (PE) is one of the commonest causes for maternal and fetal morbidity and mortality. Imbalances of angiogenic factors, oxidative stress, and inflammatory response have a role in the pathogenesis of PE. Data regarding the circulating apelin level and its role in PE remains controversial. This study was formulated to assess the serum apelin level in PE, investigate its correlation with some inflammatory, oxidative stress, and angiogenic proteins in a nitric oxide synthase inhibitor; the N (gamma)-nitro-L-arginine methyl ester (L-NAME)-induced rat model of PE and determine whether apelin administration could protect against development of PE. 40 healthy adult female albino rats and 10 adult male albino rats were used in this study. The pregnant female rats were randomly divided into three groups: group 1 (normal pregnant group), group 2 (PE-induced group), injected subcutaneously with 75 mg L-NAME/kg bodyweight/day starting from day 9 to 20 of gestation, and group 3 (PE-induced group supplemented with apelin (PE + apelin)); PE induced as before and simultaneously subcutaneously injected with apelin-13 (6 × 10−8 mol/kg bodyweight/twice daily) beginning from day 6 to 20 of gestation. In all groups, blood pressure and urine protein were determined at gestation days (GD) 0, 10, and 18. Moreover, serum apelin, placental growth factor (PLGF), vascular endothelial growth factor (VEGF), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng), interferon-gamma (IFN-γ), and interleukin-10 (IL-10) levels and serum superoxide dismutase enzyme (SOD) and catalase (CAT) activities of all groups were estimated at the end of experiment. Placental histopathological examination was also performed. PE-induced rats showed significantly decreased serum apelin levels. Moreover, they showed significantly increased blood pressures, urine proteins, sFlt-1, sEng, and IFN-γ (mean arterial blood pressure, urine proteins, sFlt-1, sEng, and IFN-γ showed significant negative correlations with serum apelin level), but it showed significantly decreased VEGF, PLGF, IL-10, SOD, and CAT (VEGF, PLGF, IL-10, and SOD showed significant positive correlations with serum apelin level). In contrast, exogenous apelin administration significantly ameliorated these parameters together with improvement in the placental histoarchitecture in the apelin-supplemented PE group. This study demonstrated the protective effects of apelin administration on the pathogenesis of PE.

Background: kisspeptin (kiss1) is a hypothalamic neuropeptide, expressed also peripherally in the placental trophoblast, pancreatic cells, liver and adipose tissue suggesting its role in regulating metabolic homeostasis as well as normal fetal implantation and placentation. There are contradictory reports about the circulating and placental levels of kiss1 during preeclampsia in either lean or obese pregnant women. Aim: This study was designed to evaluate serum and placental kiss1 levels in normotensive non-pregnant, pregnant and preeclamptic females and to detect any potential association of those levels with some homeostatic parameters occurring in these conditions with and without obesity. Design: This study was conducted on 54 female subjects at the reproductive period. They were divided according to WHO classification of BMI into two equal groups: Group I (lean group with normal BMI 18.50-24.99kg/m 2 ), and Group II (obese group with BMI 30 -34.99 kg/m) 2 , each group was subdivided into: normotensive non-pregnant group, normotensive pregnant group and preeclamptic group. Moderate degree of preeclampsia was confirmed by presence of proteinuria (> 300mg/24h) and hypertension (≥150/100). Placental kiss1 and serum kiss1, insulin, glucose, lipid profile, TNF-α, urea, creatinine and sex hormones levels were measured. BMI and HOMA-IR were calculated in all groups. Results: Serum and placental kiss1 levels were significantly higher in normotensive pregnant while these levels were significantly lower in preeclamptic than normotensive pregnant groups and this decrease was more pronounced in obese than lean subjects. Kiss1 negatively correlated with blood pressure, BMI, glucose, insulin, HOMA-IR, TC, TG, LDL, TNF-α and positively correlated with HDL-C, sex hormones. Conclusion:The decrease in kiss1 levels may play a role in pathogenesis of PE, and may represent a novel link between metabolic disturbance and PE in obese pregnant females since this peptide was correlated with BMI, HOMA-IR, dyslipidemia and TNF-α.

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Background: Apelin is an endogenous ligand for the G protein-coupled receptor APJ. The expression of both apelin and APJ has been detected in a variety of tissues including heart, ,ovary , placenta and uterus. It has a relaxant effect on smooth muscles of the stomach and blood vessels. However , its effect on the smooth muscle of the uterus is still controversy and its mechanism of action is not fully investigated. This study was designed to demonstrate the in vitro effects and mechanism of action of apelin on rat uterine reactivity. Methods: 60 adult albino rats (48 females and 12 males). Female rats were randomly divided into non-pregnant, pregnant (day 6 and day 19 ) and 1 st day postpartum groups. The effects of apelin (1, 10 and 100 nmol /L) on spontaneous reactivity of isolated uterine strips were studied. Also, apelin (100 nmol/L) in the presence of L-NAME, apamin and Glibenclamide was investigated. Results: Apelin exerted a significant dose dependent reduction in frequency and amplitude of spontaneous uterine contraction. This reduction was significantly more potent on day 6 than that in both non pregnant and pregnant rats on day 19. Also , it was significantly and nearly completely abolished in the presence of L-NAME, but it was significantly and partially decreased in the presence of (Apamin) and (Glibenclamide). Conclusions: Apelin has a potent utero-relaxant effect which is greater in early pregnancy compared with late pregnancy. Thus Apelin may be a promising tocolytic drug.