Prenatal endothelin or thromboxane receptor antagonism surpasses sympathoinhibition in improving cardiorenal malfunctions in preeclamptic rats

Habib, Yasser H.; Abdelhady, Sherien A.; Gowayed, Mennatallah A.; El-Deeb, Nevine M.; Darwish, Inas El Sayed; El‐Mas, Mahmoud M.

doi:10.1016/j.taap.2021.115615

Cited by 5 publications

(3 citation statements)

References 63 publications

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“…Consistent with reported clinical and experimental studies of exacerbated renal damage and morbidity and mortality in PE dams 29 , 30 , the present study demonstrated distinct functional and structural manifestations of renal injury in the L-NAME rodent model of PE. Opposite changes in urine protein (increases) and CrCl (decreases), positive hallmarks of renal damage 31 , 32 , were demonstrated in PE dams at GD20 compared with respective control rats and remained manifest till weaning (3 weeks post-labor). The excessive proteinuria has been attributed to the L-NAME-induced renal vascular wall thickening and elevated glomerular pressure 33 .…”

Section: Discussionmentioning

confidence: 97%

“…In this context, naproxen was more effective than the other two NSAIDs (celecoxib and diclofenac) in (i) rectifying biochemical and glomerular and tubular signs of renal injury caused by PE programming, and (ii) diminishing the upregulated renal levels of the arachidonate end products PGE2, PGF2α and TXA2. It is widely recognized that TXA2 and PGF2α are vitally implicated in the preeclamptic inflammatory response and consequent tissue remodeling and stiffness 31 , 35 . Moreover, a pathogenic role for PGE2 has been reported in oxidative and inflammatory damage associated with PE Moreover, a pathogenic role for PGE2 has been reported in oxidative and inflammatory damage associated with PE 36 , 37 .…”

Section: Discussionmentioning

confidence: 99%

“…(build 9). For each gene, changes in sample mRNA levels were determined using the 2 −ΔΔCt method and normalized to the reference gene 31 .…”

Section: Methodsmentioning

confidence: 99%

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The suppression of MAPK/NOX/MMP signaling prompts renoprotection conferred by prenatal naproxen in weaning preeclamptic rats

Abdelhady,

Ali,

Yacout

et al. 2023

Sci Rep

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Although nonsteroidal antiinflammatory drugs (NSAIDs) are frequently used for fever and pain during pregnancy, their possible interaction with perinatal renal injury induced by preeclampsia (PE) has not been addressed. Here, studies were undertaken in the N(gamma)-nitro-l-arginine methyl ester (l-NAME) PE model to assess the influence of gestational NSAIDs on renal damage in weaning dams. PE-evoked increments and decrements in urine protein and creatinine clearance, respectively, were intensified by celecoxib and weakened by diclofenac or naproxen. Naproxen also improved renal cloudy swelling, necrosis, and reduced glomerular area evoked by PE. The concomitant rises in renal expression of markers of oxidative stress (NOX2/4), extracellular matrix metaloproteinase deposition (MMP9), and prostanoids (PGE2, PGF2α, TXA2) were all more effectively reduced by naproxen compared with celecoxib or diclofenac. Western blotting showed tripled expression of mitogen-activated protein kinases (MAPKs; p-p38, p-JNK1, p-ERK1, p-ERK2) in PE kidneys that was overturned by all NSAIDs, with naproxen producing the largest drop in p-ERK2 expression. The PE-provoked elevation in renal expression of autophagic marker LC3 was reduced by naproxen and diclofenac, but not celecoxib. The data suggests superior effect for naproxen over other NSAIDs in rectifying preeclamptic renal injury and predisposing inflammatory, oxidative, autophagic, and fibrotic signals.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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The suppression of MAPK/NOX/MMP signaling prompts renoprotection conferred by prenatal naproxen in weaning preeclamptic rats

Abdelhady,

Ali,

Yacout

et al. 2023

Sci Rep

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Modulation by antenatal therapies of cardiovascular and renal programming in male and female offspring of preeclamptic rats

Habib

Gowayed

Abdelhady

et al. 2021

Naunyn-Schmiedeberg's Arch Pharmacol

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Morbidity and mortality risks are enhanced in preeclamptic (PE) mothers and their offspring. Here, we asked if sexual dimorphism exists in (i) cardiovascular and renal damage evolved in offspring of PE mothers, and (ii) offspring responsiveness to antenatal therapies. PE was induced by administering N G -nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day, oral gavage) to pregnant rats for 7 days starting from gestational day 14. Three therapies were co-administered orally with L-NAME, atrasentan (endothelin ETA receptor antagonist), terutroban (thromboxane A2 receptor antagonist, TXA2), or α-methyldopa (α-MD, central sympatholytic drug). Cardiovascular and renal profiles were assessed in 3-month-old offspring. Compared with offspring of non-PE rats, PE offspring exhibited elevated systolic blood pressure and proteinuria and reduced heart rate and creatinine clearance (CrCl). Apart from a greater bradycardia in male offspring, similar PE effects were noted in male and female offspring. While terutroban, atrasentan, or α-MD partially and similarly blunted the PE-evoked changes in CrCl and proteinuria, terutroban was the only drug that virtually abolished PE hypertension. Rises in cardiorenal inflammatory (tumor necrosis factor alpha, TNFα) and oxidative (isoprostane) markers were mostly and equally eliminated by all therapies in the two sexes, except for a greater dampening action of atrasentan, compared with α-MD, on tissue TNFα in female offspring only. Histopathologically, antenatal terutroban or atrasentan was more effective than α-MD in rectifying cardiac structural damage, myofiber separation, and cytoplasmic alterations, in PE offspring. The repair by antenatal terutroban or atrasentan of cardiovascular and renal anomalies in PE offspring is mostly sex-independent and surpasses the protection offered by α-MD, the conventional PE therapy.

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Hepatoprotective effect of prenatal celecoxib in weaning preeclamptic rats: Role of HMGB1/MAPKs signaling

Abdelhady,

Abuiessa,

Elhamammy

et al. 2024

European Journal of Pharmacology

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Prenatal endothelin or thromboxane receptor antagonism surpasses sympathoinhibition in improving cardiorenal malfunctions in preeclamptic rats

Cited by 5 publications

References 63 publications

The suppression of MAPK/NOX/MMP signaling prompts renoprotection conferred by prenatal naproxen in weaning preeclamptic rats

The suppression of MAPK/NOX/MMP signaling prompts renoprotection conferred by prenatal naproxen in weaning preeclamptic rats

Modulation by antenatal therapies of cardiovascular and renal programming in male and female offspring of preeclamptic rats

Hepatoprotective effect of prenatal celecoxib in weaning preeclamptic rats: Role of HMGB1/MAPKs signaling

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