Gestational NSAIDs distinctly reprogram cardiac injury in preeclamptic rats: Roles of cyclooxygenase, apoptotic and autophagic trails

Ali, Mennatallah A., Abdelhady, Sherien A., Yacout, Dalia M., Kandil, Lamia S. ORCID:, Elblehi, Samar S. and El-Mas, Mahmoud M. (2022) Gestational NSAIDs distinctly reprogram cardiac injury in preeclamptic rats: Roles of cyclooxygenase, apoptotic and autophagic trails. Life Sciences, 310. ISSN 0024-3205

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Aims: Considering the role of cyclooxygenases (COX) in placental programming induced by preeclampsia (PE), we investigated whether gestational exposure to nonsteroidal antiinflammatory drugs (NSAIDs) with different COX-1/2 selectivity would variably modulate pre- and postnatal (weaning time, i.e. 3 weeks after delivery) cardiovascular manifestations of PE. Materials and methods: PE was induced by oral administration of Nω-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day for 7 days) to pregnant rats starting from day 14 of gestation. Rats were treated simultaneously with celecoxib (10 mg/kg/day), diclofenac (0.5 mg/kg/day), or naproxen (1 mg/kg/day). Key findings: Tail-cuff measurements revealed a higher systolic blood pressure (SBP) in PE mothers at gestational day 20 (GD20). More exaggerated rises in prenatal SBP were noted in PE rats treated with celecoxib but not diclofenac or naproxen. Higher levels of serum creatine and kinase MB (CK-MB), a biomarker of cardiac damage, were demonstrated in weaning PE rats and this effect was suppressed by naproxen only. Additionally, naproxen was the most effective among all 3 NSAIDs in diminishing the PE-induced surges in (i) cardiomyocyte cross-sectional area, (ii) cardiac COX-1/COX-2 activities, (iii) arachidonate metabolites (PGE2, PGF2α, and TXA2), (iv) caspase-3 and beclin-1 expressions. By contrast, the PE-related increments in cardiac expression of antiangiogenic (sFlt-1, and endoglin-1) and inflammatory (nuclear factor kappa B, NF-κB) factors were indiscriminately reduced by all NSAIDs. Significance: Compared with celecoxib or diclofenac, naproxen appears to be the most advantageous in minimizing cardiac damage in weaning PE rats due to its synchronized downregulatory effects on cyclooxygenase, apoptotic, and autophagic pathways.

Item Type: Article
Uncontrolled Keywords: cardiac damage,celecoxib (pubchem cid: 2662),diclofenac potassium (pubchem cid: 23667642),n -nitro-l-arginine methyl ester (cid 135512460),nsaids,naproxen (cid 77557160),preeclampsia,biochemistry, genetics and molecular biology(all),pharmacology, toxicology and pharmaceutics(all) ,/dk/atira/pure/subjectarea/asjc/1300
Faculty \ School: Faculty of Science > School of Biological Sciences
UEA Research Groups: Faculty of Science > Research Groups > Biosciences Teaching and Education Research
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Depositing User: LivePure Connector
Date Deposited: 21 Mar 2023 09:34
Last Modified: 21 Aug 2023 01:25
DOI: 10.1016/j.lfs.2022.121130

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