scholarly journals Malaria in pregnancy regulates P‐glycoprotein (P‐gp/ Abcb1a ) and ABCA1 efflux transporters in the Mouse Visceral Yolk Sac

2020 ◽  
Vol 24 (18) ◽  
pp. 10636-10647 ◽  
Author(s):  
Lilian M. Martinelli ◽  
Klaus N. Fontes ◽  
Mila W. Reginatto ◽  
Cherley B. V. Andrade ◽  
Victoria R. S. Monteiro ◽  
...  
2020 ◽  
Author(s):  
Lilian M. Martinelli ◽  
Klaus N. Fontes ◽  
Mila W. Reginatto ◽  
Cherley B. V. Andrade ◽  
Victoria R. S. Monteiro ◽  
...  

AbstractMalaria in pregnancy (MiP) induces intrauterine growth restriction (IUGR) and preterm labor (PTL). However, its effects on yolk sac morphology and function are largely unexplored. We hypothesized that MiP modifies yolk sac morphology and efflux transport potential by modulating ABC efflux transporters. C57BL/6 mice injected with Plasmodium berghei ANKA (5×105 infected-erythrocytes) at gestational day (GD) 13.5, were subjected to yolk sac membrane harvesting at GD18.5 for histology, qPCR and immunohistochemistry. MiP did not alter the volumetric proportion of the yolk sac’s histological components. However, it increased levels of Abcb1a mRNA (encoding P-glycoprotein) and macrophage migration inhibitory factor (Mif-chemokine), whilst decreasing Abcg1 (P<0.05); without altering Abca1, Abcb1b, Abcg2, Snat1, Snat2, interleukin (Il)-1 β and C-C Motif Chemokine Ligand 2 (Ccl2). Transcripts of Il-6, chemokine (C-X-C motif) ligand 1 (Cxcl1), Glut1 and Snat4 were not detectible. ABCA1, ABCG1, breast cancer resistance protein (BCRP) and P-gp, were primarily immunolocalized to the cell membranes and cytoplasm of endodermic epithelium but also in the mesothelium and in the endothelium of mesodermic blood vessels. Intensity of P-gp labeling was stronger in both endodermic epithelium and mesothelium, whereas ABCA1 labeling increased in the endothelium of the mesodermic blood vessels. The presence of ABC transporters in the yolk sac wall suggest that this fetal membrane acts as an important protective gestational barrier. Changes in ABCA1 and P-gp in MiP may alter the biodistribution of toxic substances, xenobiotics, nutrients and immunological factors within the fetal compartment and participate in the pathogenesis of malaria induced-IUGR and PTL.


Placenta ◽  
2019 ◽  
Vol 83 ◽  
pp. e30
Author(s):  
Lilian M. Martinelli ◽  
Klaus N. Fontes ◽  
Mila W. Reginatto ◽  
Cherley B.V. Andrade ◽  
Victoria R.S. Monteiro ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Li-rui Sun ◽  
Qiu-shi Guo ◽  
Wei Zhou ◽  
Min Li

AbstractChinese herbal medicine is widely used because it has a good safety profile and few side effects. However, the risk of adverse drug reactions caused by herb-drug interactions (HDIs) is often overlooked. Therefore, the task of identifying possible HDIs and elucidating their mechanisms is of great significance for the prevention and treatment of HDI-related adverse reactions. Since extract from Dioscorea bulbifera L. rhizomes (DB) can cause various degrees of liver damage, it is speculated that HDIs may occur between DB extract and chemicals metabolized or excreted by the liver. Our study revealed that the cardiotoxicity of pirarubicin (THP) was increased by co-administration of DB, and the expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (Mrp2) in the liver was inhibited by DB extract, which led to the accumulation of THP in heart tissue. In conclusion, there are risks of the co-administration of DB extract and THP. The mechanism of HDIs can be better revealed by targeting the efflux transporters.


2016 ◽  
Vol 11 (5) ◽  
pp. 1934578X1601100 ◽  
Author(s):  
Nuno Silva ◽  
Lígia Salgueiro ◽  
Ana Fortuna ◽  
Carlos Cavaleiro

Drug efflux transporters such as P-glycoprotein (P-gp) help maintain cellular homeostasis but are also major contributors to the development of multidrug resistance (MDR) phenomena. Since P-gp was associated with MDR, several compounds showing potential to inhibit this transporter have been identified. Particular attention has been given to natural products, namely those of plant origin, looking for highly effective and safe P-gp inhibitors with little to no interaction with other cellular or metabolic processes. Here we abridge several examples of plant compounds from distinct classes, polyketides, lignans, anthraquinones, coumarins, alkaloids, mono- and sesqui-terpenes, steroids and limonoids, which have shown the ability to modulate in vitro or in vivo the P-gp activity.


Author(s):  
William P. Jollie

A technique has been developed for visualizing antibody against horseradish peroxidase (HRP) in rat visceral yolk sac, the placental membrane across which passive immunity previously has been shown to be transferred from mother to young just prior to birth. Female rats were immunized by injecting both hind foot pads with 1 mg HRP emulsified in complete Freund's adjuvant. They were given a booster of 0.5mg HRP in 0.1 ml normal saline i.v. after one week, then bred and autopsied at selected stages of pregnancy, viz., 12, 1 7 and 22 days post coitum, receiving a second booster, injected as above, five days before autopsy. Yolk sacs were removed surgically and fixed immediately in 2% paraformaldehye, 1% glutaraldehye in 0.1 M phosphate buffer with 0.01% CaCl2 at pH 7.4, room temperature, for 3 hr, rinsed 3X in 0.1 M phosphate buffer plus 5% sucrose, then exposed to 1 mg HRP in 1 ml 0.1 M phosphate buffer at pH 7.4 for 1 hr. They were refixed in aldehydes, as above, for 1 5 min (to assure binding of antigen-antibody complex). Following buffer washes, the tissues were incubated in 3 mg diaminobenzidine tetrahydrochloride and 0.01% H2O2 in 0.05 M Tris-HCl buffer for 30 min. After brief buffer washes, they were postfixed in 2% OsO4. in phosphate buffer at pH 7.4, 4°C for 2 hr, dehydrated through a graded series of ethanols, and embedded in Durcupan. Thin sections were observed and photographed without contrast-enhancement with heavy metals. Cytochemical reaction product marked the site of HRP (i.e., antigen) which, in turn, was present only where it was bound with anti-HRP antibody.


2019 ◽  
Author(s):  
Sangshin Park ◽  
Christina E. Nixon ◽  
Olivia Miller ◽  
Nam-Kyong Choi ◽  
Jonathan D. Kurtis ◽  
...  

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