1. Protective effect of leukotriene receptor antagonist, montelukast, against cyclophosphamide-induced placental toxicity via modulation of NLRP3/IL-1β signaling pathway in rats.
- Author
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Yehia Abdelzaher W, Abdeltwab Ibrahim S, Abdel-Wakeel Abdel-Gaber S, Rady Fadl R, Amgad Mohamed N, Sedik WF, and Mohamed Abdel-Aziz A
- Subjects
- Animals, Female, Pregnancy, Rats, Placenta Growth Factor metabolism, Oxidative Stress drug effects, Inflammasomes metabolism, Apoptosis drug effects, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, NLR Family, Pyrin Domain-Containing 3 Protein antagonists & inhibitors, Cyclopropanes, Cyclophosphamide toxicity, Cyclophosphamide adverse effects, Quinolines pharmacology, Quinolines therapeutic use, Acetates therapeutic use, Acetates pharmacology, Interleukin-1beta metabolism, Placenta drug effects, Placenta pathology, Placenta metabolism, Leukotriene Antagonists pharmacology, Leukotriene Antagonists therapeutic use, Signal Transduction drug effects, Sulfides, Rats, Wistar
- Abstract
Backgrounds & Aim: Placental insufficiency is a serious complication that affects pregnancy and fetal growth. Cyclophosphamide (CYC) is considered one of the chemotherapeutic agents. Unfortunately, CYC not only affects tumor cells but also affects healthy cells causing multiple injuries including the placenta. The present study aimed to evaluate the effect of cysteinyl leukotriene receptor antagonist; montelukast (MK), on CYC-induced placental injury in rats., Materials and Methods: Forty-eight female Wister rats were randomly divided into 8 experimental groups. Group 1: control pregnant group; Group 2: MK 5 mg-treated pregnant rats; Group 3: MK 10 mg-treated pregnant rats; Group 4: MK 20 mg-treated pregnant rats; Group 5: pregnant rats received CYC (20 mg/kg, i.p); Group 6: pregnant rats received MK 5 mg and CYC; Group 7: pregnant rats received MK 10 mg and CYC; Group 8: pregnant rats received MK 20 mg and CYC. Placental malondialdehyde (MDA), reduced glutathione (GSH), total antioxidant capacity (TAC), placental growth factor (PlGF), and Nod-like receptor p3 (NLRP3) inflammasome were measured. Histological changes, interleukin-1β (IL-1β), and cleaved caspase-3 immuno-expressions were also evaluated., Results: CYC showed a significant decrease in placental GSH, TAC, and PlGF with a significant increase in placental MDA, NLRP3, and immuno-expression of IL-1β and caspase-3. MK showed significant improvement in all oxidative stress (MDA, GSH and TAC), inflammatory (NLRP3 and IL-1β), and apoptotic (caspase-3) parameters., Conclusion: According to the findings, MK was proved to have a possible protective role in CYC-induced placental injury via modulation of NLRP3/IL-1β signaling pathway with anti-oxidant, anti-inflammatory, and anti-apoptotic effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
- Published
- 2024
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