Leukotriene Receptor Antagonist, Montelukast Ameliorates L-NAME-Induced Pre-eclampsia in Rats through Suppressing the IL-6/Jak2/STAT3 Signaling Pathway

Abstract

Aims: To investigate the potential protective role of montelukast (Mont) in the pre-eclampsia rat model induced by L-NG-Nitro arginine methyl ester (L-NAME). Methods and materials: Thirty-two pregnant female albino Wistar rats were assigned to four groups: the control group: pregnant rats received vehicles; the Mont group: pregnant rats received Mont (10 mg/kg/day, p.o.) from the 6th to the 18th day of gestation; the L-NAME group: pregnant rats received L-NAME (50 mg/kg/day, i.p.) from the 9th to the 18th day of gestation; the Mont/L-NAME group: pregnant rats received Mont (10 mg/kg/day, p.o.) from the 6th to the 18th day of gestation and L-NAME (50 mg/kg/day, i.p.) from the 9th to the 18th day of gestation. Placental, hepatic, and renal malondialdehyde (MDA), total nitrites (NOx), interleukin 6 (IL-6), and tumor necrosis factor (TNF)-α were determined. Serum alanine transaminase (ALT), aspartate transaminase (AST), creatinine, urea, 24-h urinary protein, and the placental growth factor (PGF) were measured. Histopathological examinations of the placental, hepatic, and renal tissues were also performed. In addition, placental, hepatic, and renal Janus kinase 2 (Jak2) and signal transducer and activator of transcription 3 (STAT3) immunoblotting were performed. Key findings: Mont improves oxidative stress, IL-6, TNF-α, ALT, AST, creatinine, urea, 24-h urinary protein, PGF, Jak2, and STAT3 which were all affected by L-NAME. Moreover, the histopathological assessment indicated that Mont restored the normal architecture that was markedly disturbed by L-NAME. Significance: Mont exerted the biochemical and histopathological amelioration of L-NAME-caused pre-eclampsia through its anti-inflammatory, anti-oxidant function and suppression of the IL-6/Jak2/STAT3 signaling pathway.

Identification of biomarkers and sex differences in the placenta of fetal growth restriction

“…According to previous studies, FOXO3 depletion leads to reduced migration and invasion of trophoblast cells, arrested cell cycle in G1 phase, and increased apoptosis under oxidative stress 37 . JAK/STAT3 pathway is indispensable for the regulation of the invasion of trophoblast and spiral artery remodeling, significant histopathological alterations in the placenta 38 . Elevated levels of soluble AXL indicate placental endothelial dysfunction by regulating critical angiogenic molecules 39 .…”

“…37 JAK/STAT3 pathway is indispensable for the regulation of the invasion of trophoblast and spiral artery remodeling, significant histopathological alterations in the placenta. 38 Elevated levels of soluble AXL indicate placental endothelial dysfunction by regulating critical angiogenic molecules. 39 BCL2L1 can be inhibited by let-7a in trophoblasts, leading to early-onset severe PE.…”

Clinical study on the difference in intestinal microecology between patients with preeclampsia and pregnant women at different stages of pregnancy

“…The inhibition of WBC function during pregnancy was related to the inhibition of humoral-cellular immune regulation function. Due to the poor ability of N denaturation, WBC is detained in the capillary in the low perfusion area of the thrombosis site, which releases lysosomes, histamines, leukotrienes, and other substances that are harmful to blood flow, resulting in microcirculation blood flow disorder ( Moodley et al, 2020 ; Abdelzaher et al, 2022 ). The etiology theory of hypertensive disorder complicating pregnancy also believes that the abnormal immune regulation function and the toxic effect of oxidative stress reaction ultimately lead to N inflammatory infiltration.…”

A network pharmacology study on mechanism of resveratrol in treating preeclampsia via regulation of AGE-RAGE and HIF-1 signalling pathways

“…The results showed that they all had good binding with RSV except STAT3. However, a recent study has demonstrated that the IL6/Jak2/STAT3 signaling pathway is involved in the development of PE ( 63 ). These results finally indicated that these six targets might be the targets of RSV against PE, and more experimental and clinical studies are still needed in the future.…”