Multidrug Resistance-Associated Protein 2 Deficiency Aggravates Estrogen-Induced Impairment of Bile Acid Metabolomics in Rats

Faradonbeh, Fatemeh Alaei; Lastuvkova, Hana; Cermanova, Jolana; Hroch, M; Nová, Zuzana; Uher, Martin; Hirsova, Petra; Pávek, Petr; Mičuda, Stanislav

doi:10.3389/fphys.2022.859294

Cited by 5 publications

(2 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It may contribute to reverse BA transport back to plasma by increased intrahepatic BA content. Biliary secretion of BAs may still be maintained by alternative canalicular BA transporter such as Mrp2 ( Alaei Faradonbeh et al, 2022 ), which was not changed by labetalol (unpublished observation). Taken together, we suggest that the upregulation of Mrp4 is the principal mechanism of increased BA plasma concentrations by labetalol in the estrogen model of ICP.…”

Section: Discussionmentioning

confidence: 94%

Labetalol and soluble endoglin aggravate bile acid retention in mice with ethinylestradiol-induced cholestasis

et al. 2023

Self Cite

View full text Add to dashboard Cite

Labetalol is used for the therapy of hypertension in preeclampsia. Preeclampsia is characterized by high soluble endoglin (sEng) concentration in plasma and coincides with intrahepatic cholestasis during pregnancy (ICP), which threatens the fetus with the toxicity of cumulating bile acids (BA). Therefore, we hypothesized that both labetalol and increased sEng levels worsen BA cumulation in estrogen-induced cholestasis. C57BL/6J, transgenic mice overexpressing human sEng, and their wild-type littermates were administrated with ethinylestradiol (EE, 10 mg/kg s.c., the mice model of ICP) and labetalol (10 mg/kg s.c.) for 5 days with sample collection and analysis. Plasma was also taken from healthy pregnant women and patients with ICP. Administration of labetalol to mice with EE cholestasis aggravated the increase in BA plasma concentrations by induction of hepatic Mrp4 efflux transporter. Labetalol potentiated the increment of sEng plasma levels induced by estrogen. Increased plasma levels of sEng were also observed in patients with ICP. Moreover, increased plasma levels of human sEng in transgenic mice aggravated estrogen-induced cholestasis in labetalol-treated mice and increased BA concentration in plasma via enhanced reabsorption of BAs in the ileum due to the upregulation of the Asbt transporter. In conclusion, we demonstrated that labetalol increases plasma concentrations of BAs in estrogen-induced cholestasis, and sEng aggravates this retention. Importantly, increased sEng levels in experimental and clinical forms of ICPs might present a novel mechanism explaining the coincidence of ICP with preeclampsia. Our data encourage BA monitoring in the plasma of pregnant women with preeclampsia and labetalol therapy.

show abstract

Section: Discussionmentioning

confidence: 94%

Labetalol and soluble endoglin aggravate bile acid retention in mice with ethinylestradiol-induced cholestasis

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…It has been a useful tool for discovering and developing biomarkers for various human diseases. The current review collected a total of 16 metabolomics studies of ICP (38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53), including 7 untargeted and 9 targeted studies (Table 3). Mass spectrometry is also the basic technology of metabolomics.…”

Section: Metabolomics Strategiesmentioning

confidence: 99%

An omics review and perspective of researches on intrahepatic cholestasis of pregnancy

Wang,

Chen,

et al. 2024

Front. Endocrinol.

View full text Add to dashboard Cite

Intrahepatic cholestasis of pregnancy (ICP) is one of the common pregnancy complications that may threaten the health of both pregnant women and their fetuses. Hence, it is of vital importance to identify key moleculars and the associated functional pathways of ICP, which will help us to better understand the pathological mechanisms as well as to develop precise clinical biomarkers. The emerging and developing of multiple omics approaches enable comprehensive studies of the genome, transcriptome, proteome and metabolome of clinical samples. The present review collected and summarized the omics based studies of ICP, aiming to provide an overview of the current progress, limitations and future directions. Briefly, these studies covered a broad range of research contents by the comparing of different experimental groups including ICP patients, ICP subtypes, ICP fetuses, ICP models and other complications. Correspondingly, the studied samples contain various types of clinical samples, in vitro cultured tissues, cell lines and the samples from animal models. According to the main research objectives, we further categorized these studies into two groups: pathogenesis and diagnosis analyses. The pathogenesis studies identified tens of functional pathways that may represent the key regulatory events for the occurrence, progression, treatment and fetal effects of ICP. On the other hand, the diagnosis studies tested more than 40 potential models for the early-prediction, diagnosis, grading, prognosis or differential diagnosis of ICP. Apart from these achievements, we also evaluated the limitations of current studies, and emphasized that many aspects of clinical characteristics, sample processing, and analytical method can greatly affect the reliability and repeatability of omics results. Finally, we also pointed out several new directions for the omics based analyses of ICP and other perinatal associated conditions in the future.

show abstract

Impact of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) on the expression and function of hepatobiliary transporters: A comprehensive mechanistic review

Laddha,

Dzielak,

Lewis

et al. 2024

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

View full text Add to dashboard Cite

Multidrug Resistance-Associated Protein 2 Deficiency Aggravates Estrogen-Induced Impairment of Bile Acid Metabolomics in Rats

Cited by 5 publications

References 56 publications

Labetalol and soluble endoglin aggravate bile acid retention in mice with ethinylestradiol-induced cholestasis

Labetalol and soluble endoglin aggravate bile acid retention in mice with ethinylestradiol-induced cholestasis

An omics review and perspective of researches on intrahepatic cholestasis of pregnancy

Impact of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) on the expression and function of hepatobiliary transporters: A comprehensive mechanistic review

Contact Info

Product

Resources

About