Pharmacological Correction of Cisplatin-Induced Hemostatic Disorders

Филонова, М. В.; Федорова, Е. П.; Чурин, А. А.; Kotlovskaya, L Yu; Solov’ev, M. A.; Удут, В. В.

doi:10.1007/s10517-021-05119-1

Cited by 3 publications

(1 citation statement)

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“…In contrast, warfarin commonly can provoke the hypocoagulation in that model ( Mira et al, 2017 ). In another mice model for the evaluation of antiplatelet and anticoagulant activities of Angelica shikokiana extract, bergapten was found to be one of the main coumarins against adenosine 5′-diphosphate-induced platelet aggregation ( Filonova et al, 2021 ). To date, no studies have been reported on the potential DDIs between the furocoumarin bergapten and PAH treatment drug macitentan.…”

Section: Introductionmentioning

confidence: 99%

Effects of bergapten on the pharmacokinetics of macitentan in rats both in vitro and in vivo

Zhou

Hou

et al. 2023

Front. Pharmacol.

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Macitentan was approved by the United States Food and Drug Administration (FDA) in 2013 for the treatment of pulmonary arterial hypertension (PAH). Bergapten is a furanocoumarin that is abundant in Umbelliferae and Rutaceae plants and is widely used in many Chinese medicine prescriptions. Considering the possible combination of these two compounds, this study is aimed to investigate the effects of bergapten on the pharmacokinetics of macitentan both in vitro and in vivo. Rat liver microsomes (RLMs), human liver microsomes (HLMs), and recombinant human CYP3A4 (rCYP3A4) were used to investigate the inhibitory effects and mechanisms of bergapten on macitentan in vitro. In addition, pharmacokinetic parameters were also studied in vivo. Rats were randomly divided into two groups (six rats per group), with or without bergapten (10 mg/kg), and pretreated for 7 days. An oral dose of 20 mg/kg macitentan was administered to each group 30 min after bergapten or 0.5% CMC-Na administration on day 7. Blood was collected from the tail veins, and the plasma concentrations of macitentan and its metabolites were assessed by ultra-performance liquid chromatography - tandem mass spectrometer (UPLC-MS/MS). Finally, we analyzed the binding force of the enzyme and two small ligands by in silico molecular docking to verify the inhibitory effects of bergapten on macitentan. The in vitro results revealed that the IC50 values for RLMs, HLMs, and rCYP3A4 were 3.84, 17.82 and 12.81 μM, respectively. In vivo pharmacokinetic experiments showed that the AUC(0-t), AUC(0-∞), and Cmax of macitentan in the experimental group (20,263.67 μg/L*h, 20,378.31 μg/L*h and 2,999.69 μg/L, respectively) increased significantly compared with the control group (7,873.97 μg/L*h, 7,897.83 μg/L*h and 1,339.44 μg/L, respectively), while the CLz/F (1.07 L/h/kg) of macitentan and the metabolite-parent ratio (MR) displayed a significant decrease. Bergapten competitively inhibited macitentan metabolism in vitro and altered its pharmacokinetic characteristics in vivo. Further molecular docking analysis was also consistent with the experimental results. This study provides a reference for the combined use of bergapten and macitentan in clinical practice.

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Section: Introductionmentioning

confidence: 99%

Effects of bergapten on the pharmacokinetics of macitentan in rats both in vitro and in vivo

Zhou

Hou

et al. 2023

Front. Pharmacol.

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Xanthotoxin (8‐methoxypsoralen): A review of its chemistry, pharmacology, pharmacokinetics, and toxicity

Zhong

et al. 2022

Phytotherapy Research

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Xanthotoxin (XAT) is a natural furanocoumarins, a bioactive psoralen isolated from the fruit of the Rutaceae plant Pepper, which has received increasing attention in recent years due to its wide source and low cost. By collecting and compiling literature on XAT, the results show that XAT exhibits significant activity in the treatment of various diseases, including neuroprotection, skin repair, osteoprotection, organ protection, anticancer, antiinflammatory, antioxidative stress and antibacterial. In this paper, we review the pharmacological activity and potential molecular mechanisms of XAT for the treatment of related diseases. The data suggest that XAT can mechanistically induce ROS production and promote apoptosis through mitochondrial or endoplasmic reticulum pathways, regulate NF‐κB, MAPK, JAK/STAT, Nrf2/HO‐1, MAPK, AKT/mTOR, and ERK1/2 signaling pathways to exert pharmacological effects. In addition, the pharmacokinetics properties and toxicity of XAT are discussed in this paper, further elucidating the relationship between structure and efficacy. It is worth noting that data from clinical studies of XAT are still scarce, limiting the use of XAT in the clinic, and in the future, more in‐depth studies are needed to determine the clinical efficacy of XAT.

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