Dataset Information

Pentoxifylline as a therapeutic option for pre-eclampsia: a study on its placental effects.

ABSTRACT:

Background and purpose

Recently pentoxifylline, a non-selective phosphodiesterase inhibitor and adenosine receptor antagonist, has attracted much interest for the treatment of the increased vascular resistance and endothelial dysfunction in pre-eclampsia. We therefore investigated the placental transfer, vascular effects and anti-inflammatory actions of pentoxifylline in healthy and pre-eclamptic human placentas.

Experimental approach

The placental transfer and metabolism of pentoxifylline were studied using ex vivo placenta perfusion experiments. In wire myography experiments with chorionic plate arteries, pentoxifyllines vasodilator properties were investigated, focusing on the cGMP and cAMP pathways and adenosine receptors. Its effects on inflammatory factors were also studied in placental explants.

Key results

Pentoxifylline transferred from the maternal to foetal circulation, reaching identical concentrations. The placenta metabolized pentoxifylline into its active metabolite lisofylline (M1), which was released into both circulations. In healthy placentas, pentoxifylline potentiated cAMP- and cGMP-induced vasodilation, as well as causing vasodilation by adenosine A₁ antagonism and via NO synthase and PKG. Pentoxifylline also reduced inflammatory factors secretion. In pre-eclamptic placentas, we observed that its vasodilator capacity was preserved, however not via NO-PKG but likely through adenosine signalling. Pentoxifylline neither potentiated vasodilation through cAMP and cGMP, nor suppressed the release of inflammatory factors from these placentas.

Conclusion and implications

Pentoxifylline is transferred across and metabolized by the placenta. Its beneficial effects on the NO pathway and inflammation are not retained in pre-eclampsia, limiting its application in this disease, although it could be useful for other placenta-related disorders. Future studies might focus on selective A₁ receptor antagonists as a new treatment for pre-eclampsia.

SUBMITTER: Broekhuizen M

PROVIDER: S-EPMC9804511 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Pentoxifylline as a therapeutic option for pre-eclampsia: a study on its placental effects.

Broekhuizen Michelle M de Vries Rene R Smits Marja A W MAW Dik Willem A WA Schoenmakers Sam S Koch Birgit C P BCP Merkus Daphne D Reiss Irwin K M IKM Danser A H Jan AHJ Simons Sinno H P SHP Hitzerd Emilie E

British journal of pharmacology 20220805 22

<h4>Background and purpose</h4>Recently pentoxifylline, a non-selective phosphodiesterase inhibitor and adenosine receptor antagonist, has attracted much interest for the treatment of the increased vascular resistance and endothelial dysfunction in pre-eclampsia. We therefore investigated the placental transfer, vascular effects and anti-inflammatory actions of pentoxifylline in healthy and pre-eclamptic human placentas.<h4>Experimental approach</h4>The placental transfer and metabolism of pento ...[more]

PMID: 35861684

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Dataset Information

Pentoxifylline as a therapeutic option for pre-eclampsia: a study on its placental effects.

Background and purpose

Experimental approach

Key results

Conclusion and implications

Publications

Pentoxifylline as a therapeutic option for pre-eclampsia: a study on its placental effects.

Similar Datasets

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