Inhibition of Heme Oxygenase-1 by Zinc Protoporphyrin IX Improves Adverse Pregnancy Outcomes in Malaria During Early Gestation

The enzyme heme oxygenase-1 (HO-1) has cytoprotective effects by catalyzing the degradation of heme to produce carbon monoxide, iron and biliverdin. Furthermore, HO-1 activity has been associated with successful pregnancy. On the other hand, in the context of certain inflammatory conditions, HO-1 ca...

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Published in:Frontiers in immunology 2022-05, Vol.13, p.879158-879158
Main Authors: Cariaco, Yusmaris, Almeida, Marcos Paulo Oliveira, Araujo, Ester Cristina Borges, Briceño, Marisol Patricia Pallete, Durán-Rodriguez, Andrea Tatiana, Franco, Rodrigo Rodrigues, Espindola, Foued Salmen, Silva, Neide Maria
Format: Article
Language:English
Subjects:
Animals
Female
ferroptosis
Heme Oxygenase-1 - metabolism
HO-1
Immunology
Iron Overload
Malaria
Mice
Pregnancy
Pregnancy Outcome
Protoporphyrins
uterine natural killer cells
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Summary:The enzyme heme oxygenase-1 (HO-1) has cytoprotective effects by catalyzing the degradation of heme to produce carbon monoxide, iron and biliverdin. Furthermore, HO-1 activity has been associated with successful pregnancy. On the other hand, in the context of certain inflammatory conditions, HO-1 can induce iron overload and cell death. To investigate the role of HO-1 in gestational malaria, pregnant BALB/c mice were infected with ANKA in early, mid and late gestation. We found that malaria affected the pregnancy outcome in the three periods evaluated. However, only poor pregnancy outcomes in early pregnancy were related to HO-1 upregulation, iron overload, lipid peroxidation and necrosis of the decidua, which were prevented by HO-1 inhibition. In conclusion, HO-1 expression must be finely tuned in gestational malaria to avoid the deleterious effect of increased enzyme activity.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2022.879158