Transplacental transfer of acetaminophen in pregnant rats

Chen, Jung-Hung; Lin, I-Hsin; Sun, Chung-Kai; Yang, Ling; Hsueh, Ting-Jen; Ting, Chin-Tsung; Tsai, Tsong-Ru

doi:10.1016/j.biopha.2022.113613

Cited by 2 publications

(1 citation statement)

References 32 publications

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“…However, a more cautious approach would be necessary given that some studies reveal behavioral impacts in the offspring of dams that received paracetamol during gestation [2] . The placental barrier is breached by paracetamol due to its low molecular weight [3] , allowing around 40% of the drug's levels in the mother's bloodstream to reach the developing fetuses [4] . Hepatotoxicity in both the mother and the fetus can result from paracetamol overdoses that cross the placenta [5] .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Potential Effect of Curcumin and/or Paracetamol in Pregnant Wistar Rats and Their Fetuses

Abd El Rahman,

Ali,

Omar

2024

Egyptian Journal of Zoology

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The present study aimed to assess the potential effects of curcumin and/or paracetamol on maternal Wistar rats (Rattus norvegicus) and their fetuses during gestation. The pregnant female Wistar rats were allotted into four groups (6 rats/each group): the control group received daily/orally vehicle, curcumin (15.75 mg/kg body weight) group, paracetamol (350 mg/kg body weight) group, and the combined group received paracetamol and curcumin simultaneously during gestation (6 th -19 th days). This study measured pregnancy outcome parameters, fetal skeletal status, hepatic oxidative stress, and histological changes. The current results revealed the unsafe consequence of paracetamol on the pregnancy outcome. At the same time, it induced fetal growth retardation, hepatic histological alterations, and altered significantly (P<0.05) the maternal and fetal hepatic oxidative status. Paracetamol intake did not affect skeletal bone ossification. On the contrary, curcumin daily intake alleviated the negative impact of paracetamol and improved fetal growth parameters, restored the normal hepatic histology, decreased lipid peroxidation levels, and increased antioxidants in maternal and fetal liver tissues. In conclusion, curcumin could be approved as a protective agent that reverses the toxic effect of paracetamol during gestation. Further studies will be done to illustrate the precise mechanisms and pathways by which the curcumin can alleviate the paracetamol impact.

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Section: Introductionmentioning

confidence: 99%

Evaluation of the Potential Effect of Curcumin and/or Paracetamol in Pregnant Wistar Rats and Their Fetuses

Abd El Rahman,

Ali,

Omar

2024

Egyptian Journal of Zoology

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Transporter modulation of molnupiravir and its metabolite β-D-N4-hydroxycytidine across the blood-brain barrier in a rat

Chang,

Peng,

Lee

et al. 2023

Commun Med

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Background The antiviral drug molnupiravir is an orally bioavailable prodrug of the nucleoside analog β-D-N4-hydroxycytidine (NHC), which is used to treat coronavirus disease 2019 (COVID-19). However, there is very little information on the barrier distribution of molnupiravir. Our hypothesis is that molnupiravir and NHC can penetrate the blood‒brain barrier (BBB) into brain tissue and that nucleoside transporters (equilibrative nucleoside transporters; ENT and concentrative nucleoside transporters; CNT) can modulate this process. Methods To investigate the mechanism of molnupiravir transport through the BBB, multiple microdialyses coupled to a validated ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC‒MS/MS) was developed to monitor dialysates, and nitrobenzylthioinosine (NBMPR; an inhibitor of ENT) was administered concomitantly with molnupiravir (100 mg/kg, i.v.) in the male rat. Results Here, we show that molnupiravir is rapidly metabolized to NHC in the blood and crossed the BBB in 20 min. Furthermore, when NBMPR is concomitantly administered to inhibit efflux, the concentrations of molnupiravir and NHC in the brain increased significantly. Conclusions In summary, molnupiravir rapidly transforms into NHC and crosses the BBB and reaches the brain at approximately 0.3-0.8% of the blood‒brain ratio. The maximum concentration of NHC in the blood and brain is above the average half maximal inhibitory concentration (IC50) of the drug required to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, suggesting a therapeutic effect. The penetration of NHC is modulated by NBMPR. These findings provide constructive information on brain disorders in clinical patients with COVID-19.

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Transplacental transfer of acetaminophen in pregnant rats

Cited by 2 publications

References 32 publications

Evaluation of the Potential Effect of Curcumin and/or Paracetamol in Pregnant Wistar Rats and Their Fetuses

Evaluation of the Potential Effect of Curcumin and/or Paracetamol in Pregnant Wistar Rats and Their Fetuses

Transporter modulation of molnupiravir and its metabolite β-D-N4-hydroxycytidine across the blood-brain barrier in a rat

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