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

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 v...

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Main Authors: Walaa Yehia Abdelzaher, Gomaa Mostafa-Hedeab, Haitham Ahmed Bahaa, Ahmad Mahran, Michael Atef Fawzy, Sara Mohamed Naguib Abdel Hafez, Nermeen N. Welson, Remon Roshdy Rofaeil
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/15/8/914
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author Walaa Yehia Abdelzaher
Gomaa Mostafa-Hedeab
Haitham Ahmed Bahaa
Ahmad Mahran
Michael Atef Fawzy
Sara Mohamed Naguib Abdel Hafez
Nermeen N. Welson
Remon Roshdy Rofaeil
author_facet Walaa Yehia Abdelzaher
Gomaa Mostafa-Hedeab
Haitham Ahmed Bahaa
Ahmad Mahran
Michael Atef Fawzy
Sara Mohamed Naguib Abdel Hafez
Nermeen N. Welson
Remon Roshdy Rofaeil
author_sort Walaa Yehia Abdelzaher
collection DOAJ
description 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.
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spelling doaj.art-52283607dad74062a45745bbb008dc522023-11-30T22:09:50ZengMDPI AGPharmaceuticals1424-82472022-07-0115891410.3390/ph15080914Leukotriene Receptor Antagonist, Montelukast Ameliorates L-NAME-Induced Pre-eclampsia in Rats through Suppressing the IL-6/Jak2/STAT3 Signaling PathwayWalaa Yehia Abdelzaher0Gomaa Mostafa-Hedeab1Haitham Ahmed Bahaa2Ahmad Mahran3Michael Atef Fawzy4Sara Mohamed Naguib Abdel Hafez5Nermeen N. Welson6Remon Roshdy Rofaeil7Department of Pharmacology, Faculty of Medicine, Minia University, Minia 61511, EgyptPharmacology Department, Medical College, Jouf University, Sakaka 11564, Saudi ArabiaDepartment of Obstetrics and Gynecology, Faculty of Medicine, Minia University, Minia 61511, EgyptDepartment of Obstetrics and Gynecology, Faculty of Medicine, Minia University, Minia 61511, EgyptDepartment of Biochemistry, Faculty of Pharmacy, Minia University, Minia 61511, EgyptDepartment of Histology and Cell Biology, Faculty of Medicine, Minia University, Minia 61511, EgyptDepartment of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Beni-Suef University, Beni Suef 62511, EgyptDepartment of Pharmacology, Faculty of Medicine, Minia University, Minia 61511, EgyptAims: 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.https://www.mdpi.com/1424-8247/15/8/914leukotriene receptor antagonistL-NAMEpre-eclampsiaIL-6/Jak2/STAT3
spellingShingle Walaa Yehia Abdelzaher
Gomaa Mostafa-Hedeab
Haitham Ahmed Bahaa
Ahmad Mahran
Michael Atef Fawzy
Sara Mohamed Naguib Abdel Hafez
Nermeen N. Welson
Remon Roshdy Rofaeil
Leukotriene Receptor Antagonist, Montelukast Ameliorates L-NAME-Induced Pre-eclampsia in Rats through Suppressing the IL-6/Jak2/STAT3 Signaling Pathway
Pharmaceuticals
leukotriene receptor antagonist
L-NAME
pre-eclampsia
IL-6/Jak2/STAT3
title Leukotriene Receptor Antagonist, Montelukast Ameliorates L-NAME-Induced Pre-eclampsia in Rats through Suppressing the IL-6/Jak2/STAT3 Signaling Pathway
title_full Leukotriene Receptor Antagonist, Montelukast Ameliorates L-NAME-Induced Pre-eclampsia in Rats through Suppressing the IL-6/Jak2/STAT3 Signaling Pathway
title_fullStr Leukotriene Receptor Antagonist, Montelukast Ameliorates L-NAME-Induced Pre-eclampsia in Rats through Suppressing the IL-6/Jak2/STAT3 Signaling Pathway
title_full_unstemmed Leukotriene Receptor Antagonist, Montelukast Ameliorates L-NAME-Induced Pre-eclampsia in Rats through Suppressing the IL-6/Jak2/STAT3 Signaling Pathway
title_short Leukotriene Receptor Antagonist, Montelukast Ameliorates L-NAME-Induced Pre-eclampsia in Rats through Suppressing the IL-6/Jak2/STAT3 Signaling Pathway
title_sort leukotriene receptor antagonist montelukast ameliorates l name induced pre eclampsia in rats through suppressing the il 6 jak2 stat3 signaling pathway
topic leukotriene receptor antagonist
L-NAME
pre-eclampsia
IL-6/Jak2/STAT3
url https://www.mdpi.com/1424-8247/15/8/914
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