Antenatally Administered NSAIDs Improve Renal Cyclooxygenase and Antiangiogenic Profiles in Rats with Preeclampsia

A. Abdelhady, Sherien, Ali, Mennatallah, Yacout, Dalia, Kandil, Lamia ORCID:, Elblehi, Samar and El-Mas, Mahmoud (2021) Antenatally Administered NSAIDs Improve Renal Cyclooxygenase and Antiangiogenic Profiles in Rats with Preeclampsia. In: UNSPECIFIED.

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Although cyclooxygenase (COX) inhibitors are often prescribed to relief fever and pain during pregnancy, their possible interaction with perinatal renal injury induced by preeclampsia (PE) remains undecided. Here, functional, and molecular studies were undertaken in the L-NAME model of PE to assess the influence of gestational exposure to selective COX-2 (celecoxib) or nonselective COX-1/COX-2 inhibitors (diclofenac or naproxen) on the developed renal damage. The treatment of rats with L-NAME (50 mg/kg/day) during the last week of pregnancy significantly increased urine protein content, a marker of renal damage, at gestational day 20, an effect that continued till weaning. The proteinuric effect of PE was paradoxically affected by NSAIDS, intensified by celecoxib, and weakened by diclofenac or naproxen. All NSAIDs comparably reduced the heightened COX-2 activity in renal tissues of PE rats, whereas the parallel elevation in renal COX-1 activity was expectedly less affected by celecoxib compared with the nonselective drugs. The dramatic PE-mediated 10-fold rise in renal prostanoids (PGE2, PGF2α, and thromboxane A2) was reduced by naproxen and to a lesser extent by celecoxib. On the other hand, diclofenac had no effect on elevated renal thromboxane A2, and was less effective than other NSAIDs in reducing renal PGE2 and PGF2α. Finally, all 3 NSAIDs dampened down the elevated renal gene expression of the antiangiogenic factors fms-like tyrosine kinase-1 and soluble endoglin, key predisposing factors to PE-associated multisystem organ injury. The data demonstrate that all tested NSAIDs favorably reprogram perinatal renal damage caused by PE and predisposing molecular mechanisms, effects that were most evident with naproxen.

Item Type: Conference or Workshop Item (Other)
Faculty \ School: Faculty of Science > School of Biological Sciences
UEA Research Groups: Faculty of Science > Research Groups > Biosciences Teaching and Education Research
Depositing User: LivePure Connector
Date Deposited: 04 Jul 2022 12:30
Last Modified: 01 Jul 2024 23:42
DOI: 10.1096/fasebj.2021.35.S1.05301

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