No abstract

Preeclampsia (PE), a hypertensive disorder during pregnancy, has adverse effects to both the mother and the fetus. Maternal inflammatory and vascular endothelial dysfunction are important factors in the pathogenesis of PE. The present study aimed to investigate the effects of estradiol (E2) on inflammatory and endothelial dysfunction in an N (omega)-nitro-L-arginine methyl ester (L-NAME)-induced rat model of PE. Adult pregnant female Sprague-dawley rats were divided into four equal groups between days 7 and 11 of gestation and treated as follows: i) Pregnant rats receiving daily intraperitoneal (i.p.) injections of equal volume of 0.9% normal saline (NS) (control group, n=12); ii) pregnant rats receiving daily i.p. injections of L-NAME at 50 mg/kg (L-NAME group, n=12); iii) pregnant rats receiving a daily i.p. injection of 50 mg/kg L-NAME and NS from day 11 (L-NAME + NS group, n=12); and iv) pregnant rats receiving daily i.p. injections of 50 mg/kg L-NAME and 100 µg/kg/day E2 from day 11 (L-NAME + E2 group, n=12). On day 21, blood pressure (BP) and the level of 24-h urine protein in the maternal rats, fetal weight and percentage of stillbirths following a cesarean section were recorded. The activities of nitric oxide (NO) and inducible NO synthase (iNOS), the levels of inflammatory cytokines [interleukin (IL)-1β, IL-6, interferon-γ and monocyte chemoattractant protein-1], adherence factors (cd49d, intracellular adhesion molecule 1 and lymphocyte function-associated antigen-1) and uterine angiogenic status (Fms-like tyrosine kinase-1, vascular cell adhesion molecule and matrix metalloproteinase 2/9) were also assessed. In addition, the histopathology of the placenta, the expression of estrogen receptor α 36 (ERα36), ERα, ERβ and G protein-coupled ER, as well as the activation of the toll-like receptor 4 (TLR4) signaling pathway (TLR4, myeloid differentiation primary response 88, IL-1 receptor-associated kinase 4 and tumor necrosis factor receptor-associated factor 6) were evaluated by H&E staining, immunofluorescence and western blot assays. Treatment with L-NAME increased the BP, urine protein and rate of stillbirths and suppressed fetal weight compared with those in the control group. The L-NAME-induced effects were attenuated by the administration of E2. In addition, the administration of E2 decreased inflammation and NO levels and altered the uterine angiogenic status. The histological analysis of PE rat placenta in the E2-treated group confirmed the effects on biochemical parameters. Of note, E2 treatment significantly suppressed the TLR4 signaling pathway. In the rat model of PE, adverse outcomes including BP, fetal rat weight and proteinuria, high neonatal death rate, inflammatory response, oxidative stress and endothelial dysfunction were attenuated by exogenous E2 administration, which may present a novel approach for the clinical treatment of PE.

Septic acute kidney injury (AKI) is usually caused by sepsis. ω3 fatty acid has been reported to suppress sepsis-induced organ dysfunction to a certain degree. The present study aimed to investigate the effects of ω3 fatty acid in septic renal injury. Sprague Dawley rats were used to establish a cecal ligation and puncture (CLP) model in order to mimic the development of septic injury. The rats were treated with dexamethasone and fish oils (FOs) for 4 days prior to CLP. Alterations in the morphology of the tissues, the renal function and the induction of inflammation, oxidative stress and apoptosis were evaluated. The effects of FOs on nuclear factor-κB (NF-κB), JAK2/STAT3 and p38-MAPK were determined. The rats of the CLP model group exhibited low survival rates and increased expression of serum creatine, blood urea nitrogen, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1 and of proinflammatory cytokines. In addition, the levels of the markers of oxidative injury and apoptosis were increased. The induction of renal injury was notably reversed by administration of dexamethasone and FOs. The expression levels of the protein markers involved in inflammation and apoptosis were measured and the results indicated that FOs inhibited JAK/STAT3 and p-38MAPK signaling, while they concomitantly increased the expression of NF-κB. The present study highlighted that FOs improve CLP-induced mortality and renal injury by inhibiting inflammation, oxidative stress and apoptosis.