Chlorophyll Derivatives Exert Greater Potency Over Progesterone in the Prevention of Infection-Induced Preterm Birth in Murine Models

Preterm birth (PTB) is a significant cause of maternal and neonatal morbidity and mortality worldwide. However, the effectiveness of progesterone (P4) which is clinically used for PTB management remains controversial and necessitates research into new therapeutic options METHOD OF STUDY: In the current study, we investigated the effectiveness of two chlorophyll derivatives, pheophorbide a (PBa) and pheophytin a (PTa), in counteracting PTB. Timed-pregnant mice (gestation day 17 ± 0.5) received lipopolysaccharide (LPS) (25 µg/mouse) or phosphate-buffered saline (PBS) intraperitoneally, with PBa, PTa, progesterone (P4), and co-administration of P4 and ibuprofen (IBP), administered orally 2 h prior. The LPS group experienced PTB and 100% fetal mortality, whereas the PBa and PTa groups showed a delayed onset of LPS-induced PTB, with significantly decreased PTB rate and fetal mortality. In addition, PBa and PTa suppressed LPS-induced pro-inflammatory cytokines and NF-?B transcription factor while increasing anti-inflammatory cytokines in the placenta and uterus. Our findings indicate that the chlorophyll derivatives, PBa and PTa increase fetal survival in infection-induced PTB and demonstrate greater efficacy than P4 in preventing PTB. © 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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