scholarly journals Inhibition of Human Liver Carboxylesterase (hCE1) by Organophosphate Ester Flame Retardants and Plasticizers: Implications for Pharmacotherapy

2019 ◽  
Vol 171 (2) ◽  
pp. 396-405 ◽  
Author(s):  
Allison L Phillips ◽  
Heather M Stapleton
Keyword(s):  
Angiotensin Converting Enzyme ◽  
House Dust ◽  
Human Liver ◽  
Human Exposure ◽  
Flame Retardants ◽  
Enzyme Inhibitor ◽  
Converting Enzyme ◽  
Ic50 Values ◽  
Diphenyl Phosphate

Abstract Organophosphate ester (OPE) flame retardants and plasticizers, consumer product additives with widespread human exposure, were evaluated for their effect on the activity of purified human liver carboxylesterase (hCE1). Four of the 15 OPEs tested had IC50 values lower than 100 nM, including triphenyl phosphate (TPHP), 2-ethylhexyl diphenyl phosphate (EHDPHP), 4-isopropylphenyl diphenyl phosphate (4IPPDPP), and 4-tert-butylphenyl diphenyl phosphate (4tBPDPP), as did 4 of the commercial flame retardant mixtures tested. Because hCE1 is critical for the activation of imidapril, an angiotensin-converting enzyme-inhibitor prodrug prescribed to treat hypertension, the most potent inhibitors, TPHP and 4tBPDPP, and an environmentally relevant mixture (house dust) were further evaluated for their effect on imidapril bioactivation in vitro. TPHP and 4tBPDPP were potent inhibitors of hCE1-mediated imidapril activation (Ki = 49.0 and 17.9 nM, respectively). House dust extracts (100 µg/ml) also caused significant reductions (up to 33%) in imidapril activation. Combined, these data suggest that exposure to OPEs may affect pharmacotherapy.

Angiotensin-converting enzyme determination in plasma during therapy with converting enzyme inhibitor: two methods compared

1991 ◽  
Vol 37 (8) ◽  
pp. 1390-1393 ◽  
Author(s):  
T P Gorski ◽  
D J Campbell
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Spectrophotometric Method ◽  
Enzyme Inhibitor ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Fluorometric Method ◽  
Converting Enzyme Inhibitor ◽  
Ace Activity

Abstract For normal and above-normal concentrations of angiotensin-converting enzyme (ACE; EC 3.4.15.1) activity in plasma, results of a manual fluorometric method [with hippuryl-histidyl-leucine (HHL), 5 mmol/L, as substrate] correlated well with those of an automated spectrophotometric method [with 3-(2-furylacryloyl)-L-phenylalanyl-glycyl-glycine (FAPGG), 2 mmol/L, as substrate]. However, for patients receiving converting enzyme inhibitor (CEI) therapy, the spectrophotometric method showed much greater suppression of plasma ACE activity than did the fluorometric method. To determine which of the two methods provided a more reliable indication of ACE inhibition in vivo, we measured plasma ACE, angiotensin I (ANG I), and angiotensin II (ANG II) in patients receiving the CEI perindopril. During perindopril therapy, changes in the ratio of ANG II:ANG I, an index of ACE activity in vivo, showed a close agreement with changes in plasma ACE activity measured with FAPGG as substrate, but not with HHL as substrate. We conclude that measurement of ACE activity in vitro with FAPGG as substrate provides a reliable measure of changes in conversion of ANG I to ANG II in vivo during CEI therapy.

scholarly journals AN IN VITRO STUDY OF CINNAMOMUM ZEYLANICUM AS NATURAL INHIBITOR OF ANGIOTENSIN-CONVERTING ENZYME (ACE) ON SHEEP (OVIS ARIES) TISSUES

2016 ◽  
Vol 9 (5) ◽  
pp. 249
Author(s):  
Ranjini Hs ◽  
Padmanabha Udupa Eg ◽  
Shobha U Kamath ◽  
Manjunath Setty ◽  
Basavaraj Hadapad ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Angiotensin Converting Enzyme ◽  
Methanolic Extract ◽  
Enzyme Inhibitor ◽  
Ovis Aries ◽  
Converting Enzyme ◽  
Kinetic Assay ◽  
Natural Inhibitor ◽  
Ace Activity

ABSTRACTObjective: The present study was aimed to find the angiotensin-converting enzyme (ACE) inhibitory activity using the methanolic extract ofCinnamomum zeylanicum (as a natural inhibitor) on sheep tissues as the enzyme source.Methods: Hippuryl-histidyl-leucine (HHL) as a substrate, tissue ACE activity was measured spectrophotometrically at 228 nm. For an incubationperiod of 30 minutes at 37°C, the linearity of ACE activity of kidney, lung, and testis enzyme was established. A known medicinal plant C. zeylanicumwas used as natural inhibitor of ACE. In this enzyme assay, inhibitory effect of methanolic extract of C. zeylanicum on kidney, lung and testicular ACEwas determined. ACE activity was confirmed by captopril, a standard inhibitor of ACE.Results: In the presence of a methanolic extract of C. zeylanicum (10:1), ACE activity was determined and this has inhibited ACE activity verysignificantly. C. zeylanicum leaves extract has reduced sheep kidney, lung, and testis ACE activity by 70.06%, 12.63%, and 20.23%, respectively.Conclusion: Significant inhibition was observed in the kidney ACE than in lung and testis ACE activity. This can propose that there may be a possiblerole in controlling blood pressure or reduction in cardiovascular diseases. Some plants with the great medicinal property may be considered aspromising sources of natural inhibitors of ACE for medicine and commercial uses. This comprehensive study may show numerous beneficial effects asa potential therapeutic agent for lowering blood pressure.Keywords: Angiotensin-converting enzyme, Natural angiotensin-converting enzyme inhibitor, Kinetic assay, Hippuryl-histidyl-leucine, Cinnamomumzeylanicum, Cardiovascular diseases.

Angiotensin Converting Enzyme Activity in Human Serum: Relationship to Enzyme Inhibitor In Vivo and In Vitro

1982 ◽  
Vol 127 (2) ◽  
pp. 396-396
Author(s):  
B.N. Swanson ◽  
M. Hichens ◽  
P. Mojaverian ◽  
R.K. Ferguson ◽  
P.H. Vlasses ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Angiotensin Converting Enzyme ◽  
Human Serum ◽  
Enzyme Inhibitor ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme Activity

scholarly journals Angiotensin-Converting Enzyme Inhibitors Reduce Uterine Fibroid Incidence in Hypertensive Women

2020 ◽  
Author(s):  
Nicole M Fischer ◽  
Tim O Nieuwenhuis ◽  
Bhuchitra Singh ◽  
Gayane Yenokyan ◽  
James H Segars
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Enzyme Inhibitor ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
The United States ◽  
Population Based ◽  
Research Database ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors

Absctract Context In vitro and in vivo evidence has supported the role of angiotensin II blockade in reducing leiomyoma cell proliferation and growth. However, no population-based study to date has investigated this potential association. Objective This work aims to determine whether prior angiotensin-converting enzyme inhibitor (ACEi) use is associated with a reduced odds of leiomyoma development. Design A nested case-control study was conducted. Setting The population was assembled from the Truven Health MarketScan Research Database, which includes private health insurance claims from January 1, 2012 to December 31, 2017. Patients or Other Participants We included (n = 353 917) women age 18 to 65 with hypertension. Cases (n = 13 108) with a leiomyoma diagnosis were matched to controls (n = 340 808) with no such diagnosis at a 1:26 ratio by age and region of origin within the United States. Intervention Prior ACEi use was determined from outpatient drug claims. Main Outcome Measure Leiomyoma development was indicated by a first-time diagnosis code. Results Women on an ACEi experienced a 31.8% reduced odds of developing clinically recognized leiomyoma compared to nonusers (odds ratio [OR] 0.68; 95% CI, 0.65-0.72). This association was significant for each age group: 30 to 39 years (OR 0.86; 95% CI, 0.74-0.99), 40 to 49 years (OR 0.71; 95% CI, 0.66-0.76), 50 to 59 years (OR 0.63; 95% CI, 0.58-0.69), and 60 to 65 years (OR 0.58; 95% CI, 0.50-0.69). Of the ACEis, lisinopril (OR 0.67; 95% CI, 0.64-0.71), quinapril (OR 0.62; 95% CI, 0.41-0.92), and ramipril (OR 0.35; 95% CI, 0.23-0.50) demonstrated a significant association with reduced leiomyoma incidence. Conclusions ACEi use was associated with a reduced odds of developing clinically recognized leiomyoma in adult hypertensive women.

scholarly journals Renal endothelial function is associated with the anti-proteinuric effect of ACE inhibition in 5/6 nephrectomized rats

2016 ◽  
Vol 310 (10) ◽  
pp. F1047-F1053 ◽  
Author(s):  
Simone Vettoretti ◽  
Peter Vavrinec ◽  
Peter Ochodnicky ◽  
Leo E. Deelman ◽  
Dick De Zeeuw ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Endothelial Function ◽  
Renal Injury ◽  
Renal Damage ◽  
Enzyme Inhibitor ◽  
Ace Inhibition ◽  
Variable Degree ◽  
Converting Enzyme ◽  
Variable Response

In healthy rats, the physiological variation of baseline endothelial function of intrarenal arteries correlates with the severity of renal damage in response to a subsequent specific renal injury. However, whether such a variation in endothelial function may also condition or predict the variable response to angiotensin-converting enzyme-inhibiting treatment in these individuals has not been addressed before. To study this, 5/6 nephrectomy was performed to induce renal injury and chronic kidney disease in a group of healthy Wistar rats. At the time of nephrectomy, interlobar arteries were obtained from the extirpated right kidney and studied in vitro for endothelium-dependent relaxation to acetylcholine. Six weeks thereafter, treatment with lisinopril was started ( n = 11) and continued for 9 wk. Proteinuria (metabolic cages) and systolic blood pressure (SBP; tail cuff) were evaluated weekly, and these were analyzed in relation to renal endothelial function at baseline. 5/6 Nephrectomy induced an increase in SBP and progressive proteinuria. Treatment with lisinopril reduced SBP and slowed proteinuria, albeit to a variable degree among individuals. The acetylcholine-induced renal artery dilation at baseline negatively correlated with lisinopril-induced reduction of proteinuria ( r2 = 0.648, P = 0.003) and with the decrease in SBP ( r2 = 0.592, P = 0.006). Our data suggest that angiotensin-converting enzyme-inhibitor attenuates the progression of renal damage the most in those individuals with decreased basal renal endothelial-mediated vasodilation.

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