Transporters, enzymes, and enalapril removal in a rat (CC531-induced) liver metastatic model

2007 ◽  
Vol 293 (5) ◽  
pp. G1078-G1088 ◽  
Author(s):  
Lichuan Liu ◽  
Huadong Sun ◽  
Wiqas Y. Valji ◽  
K. Sandy Pang

Temporal changes in physiological spaces, protein expression of transporters and enzymes, and enalapril removal were appraised in the metastatic liver tumor model developed from male Wag/Rij rats after the intraportal injection of CC531 colon adenocarcinoma cells; sham-operated preparations received PBS. Liver tissue spaces, investigated with multiple indicator dilution technique in liver perfusion studies, were unchanged at week 3 after tumor induction. At week 4, however, the sinusoidal blood volume and albumin Disse space in tumor-bearing livers were slightly lower compared with those of shams. Increased levels of the canalicular ATP transporters, P-glycoprotein, multidrug resistance-associated protein 2 (Mrp2), and bile salt export pump (Bsep) at week 2 ( P < 0.05), unchanged levels of Ntcp, Oatp1a1, Oatp1a4, and Mct2, but decreased levels of cytochrome P450 3a2 (Cyp3a2) and glutathione S-transferase (Gst4-4) at week 4 ( P < 0.05) were observed in peritumor vs. sham-operated liver tissues with Western blotting. The steady-state extraction ratio of enalapril, a substrate that enters the liver rapidly via Oatp1a1 and primarily undergoes metabolism by the carboxylesterases, was unaffected by liver metastasis at week 4 regardless of its delivery via the portal vein or hepatic artery into the perfused liver preparations.

1990 ◽  
Vol 259 (1) ◽  
pp. G32-G40 ◽  
Author(s):  
K. S. Pang ◽  
F. Barker ◽  
A. J. Schwab ◽  
C. A. Goresky

The space distribution and the processes underlying uptake of tracer substrate may be appraised by the multiple indicator dilution technique, after the simultaneous injection of noneliminated vascular (51Cr-labeled red blood cells), extracellular (125I-labeled albumin and [14C]sucrose for high and low molecular weight interstitial space, respectively), and cellular (3H2O) indicators and tracer substrate. When tracer substrates and/or their metabolites containing 14C or 3H labels are being studied, it becomes necessary to find substitutions for the similarly labeled noneliminated indicators. In red blood cell-perfused rat livers, 58Co-EDTA is found to be a good replacement for the low molecular weight interstitial reference; it has a space distribution indistinguishable from that for [14C]sucrose. [14C]urea and 3H2O, which distribute similarly in red blood cells, have similar outflow dilution profiles. With corrections for minor deviations in recovery [a ratio of 0.936 +/- 0.024 (SD)] and transit time [a ratio of 0.962 +/- 0.008 (SD)], the cellular water space can be closely approximated from the [14C]-urea curve. 58Co-EDTA and [14C]urea are reasonable substitutes for [14C]sucrose and 3H2O, respectively, in multiple indicator dilution liver perfusion studies for investigating transfer and removal characteristics of tracer substrates.


1994 ◽  
Vol 161 (3) ◽  
pp. 393-406 ◽  
Author(s):  
K. Kunzelmann ◽  
I. N. Slotki ◽  
P. Klein ◽  
T. Koslowsky ◽  
D. A. Ausiello ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 564
Author(s):  
Nayara Simas Frauches ◽  
Júlia Montenegro ◽  
Thuane Amaral ◽  
Joel Pimentel Abreu ◽  
Gabriela Laiber ◽  
...  

There is a significant indication of the beneficial health effects of fruit rich diets. Fruits of native plant species have noticeably different phytochemicals and bioactive effects. The aim of this work was to characterize and compare the constituents of jabuticaba (Myrciaria jaboticaba, MJ), jamun-berry (Syzygium cumini, SC), and malay-apple (Syzygium malaccense, SM) extracts and their influence on antioxidant activity in vitro and antiproliferative effects on human colon adenocarcinoma cells. According to the results, dried peel powders (DP) have a high anthocyanin content, phenolic compounds, and antioxidant activity when compared to freeze dried extracts (FD). M. jaboticaba dried peel powder extract had a higher total anthocyanin and phenolic compounds content (802.90 ± 1.93 and 2152.92 ± 43.95 mg/100 g, respectively). A reduction in cell viability of HT-29 cells after treatment with M. jaboticaba extracts (DP-MJ and FD-MJ) was observed via MTT assay. Flow cytometry showed that the treatment with the anthocyanin-rich extracts from MJ, SC, and SM had an inhibitory impact on cell development due to G2/M arrest and caused a rise in apoptotic cells in relation to the control group. The findings of this study highlight the potential of peel powders from Myrtaceae fruits as an important source of natural antioxidants and a protective effect against colon adenocarcinoma.


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