Determining myeloperoxidase activity and protein concentration in a single assay: Utility in biomarker and therapeutic studies

Russell, Muir; Prokoph, Nina; Henderson, Neil; Eketjäll, Susanna; Balendran, Clare A.; Michaëlsson, Erik; Fidock, Mark; Hughes, Glen

doi:10.1016/j.jim.2017.07.003

Cited by 6 publications

(5 citation statements)

References 9 publications

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“…This proinflammatory enzyme is highly expressed by neutrophils and as such is widely used as a neutrophil marker. These oxidants may contribute to host tissue damage at sites of inflammation through reactions with a wide range of biological substrates, including DNA, lipids, and protein amino groups (Russell et al, 2017). In fact, it is well-known that this enzyme is increased in acetic acid induced colitis (Dembiński et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

The potential Anti-Inflammatory and antioxidant activities of Proanthocyanidins in acetic acid–induced ulcerative colitis in rats

Hussein

Zaid

Latif

et al. 2019

Benha Veterinary Medical Journal

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The present study was designed to investigate the anti-colitic effect of Proanthocyanidins (Pcs) in acetic acid -induced ulcerative colitis in rats.Forty male albino rats (220-250 g) were divided into five equal groups of 8 rats each. Group I: (Control normal group) rats received no drugs. Group II: (Early ulcerative colitis-induced group): rats received 2 ml (3% v/v) glacial acetic acid intracolonially at 21 th day from experiment and sacrificed 3 days later of acetic acid administration. Group III: (Late ulcerative colitis-induced group) rats received glacial acetic acid similar to group II for 3 successive days and sacrificed after 21 days. Group IV: (Early ulcerative colitis + Proanthocyanidins protected group) rats received Proanthocyanidins (200 mg/kg body weight/day) orally for 21 days prior to glacial acetic acid administration for 3 days, then the animals were sacrificed. Group V: (Late ulcerative colitis + Proanthocyanidins treated group) rats first administered with glacial acetic acid then after 3 days Proanthocyanidins was administered for 21 days. A significant increase in L-Malondialdehyde (L-MDA) and Myeloperoxidase (MOP) activity with marked decrease in reduced glutathione (GSH) and Catalase (CAT) activity in colon tissue of UC-induced rats as compared with control normal group. However, a significant depletion of colon tissue L-MDA, MOP activity and marked increase in GSH concentrations and CAT activity were observed after Proanthocyanidins treatment compared to ulcerated untreated rats. The quantification real time PCR (qPCR) results revealed a significant up-regulation of mRNA gene expression levels of Tumor necrosis factor alpha (TNF-α), Cyclooxygenase-2 (COX-2) and a significant down-regulation in Transforming growth factor -β1 (TGF-β1) in colon of acetic acid -induced colon ulcer in rats. The expression levels of TNF-α, COX-2 were significantly down-regulated and a significant up-regulated in TGF-β1 in colon tissues after administration of Pcs. Proanthocyanidins (Pcs) protect rats colon mucosa damage against acetic acid -induced ulcerative colitis via antiinflammatory and anti-oxidative mechanisms.

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Section: Discussionmentioning

confidence: 99%

The potential Anti-Inflammatory and antioxidant activities of Proanthocyanidins in acetic acid–induced ulcerative colitis in rats

Hussein

Zaid

Latif

et al. 2019

Benha Veterinary Medical Journal

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“…Plasma was prepared by centrifugation at 1,500 g, 4°C for 10 minutes and carefully removed to a fresh collection tube without disturbing the cell layer. The 500 µL plasma was then transferred to separate collection tubes and stored at −80°C prior to measurement of MPO activity and concentration according to the method described by Russell et al 12 …”

Section: Methodsmentioning

confidence: 99%

“…MPO concentration and activity were analysed using 100 µL undiluted plasma samples in duplicate in a single plate assay according to the method described by Russell et al [12]. MPO is a heme-containing enzyme in which the iron is oxidized from the resting ferric state to an activated two-electron oxidized form by reacting with H 2 O 2 .…”

Section: Rationale For Mpo Assessment and Quantification Of Mpo Actimentioning

confidence: 99%

“…Plasma was prepared by centrifugation at 1500g, 4 o C for 10 minutes and carefully removed to a fresh collection tube without disturbing the cell layer. 500 µL plasma was then transferred to separate collection tubes and stored at -80 o C prior to measurement of MPO activity and concentration according to the method described by Russell et al[12].Serum samples for measurement of uric acid were collected pre-dose, 2, 4, 6, 8 and 12 hours post first and last dose. In addition, pre-dose day 2 to day 9 (to day 13 at 10 mg) and 24, 36, 48, 96, 144, 240 and 336 hours post last dose.…”

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confidence: 99%

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Early Clinical Experience With AZD4831, A Novel Myeloperoxidase Inhibitor, Developed for Patients With Heart Failure With Preserved Ejection Fraction

Nelander

Lagerström-Fermér

Amilon

et al. 2021

Clinical Translational Sci

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We evaluated safety, tolerability, pharmacokinetics and pharmacodynamics of AZD4831, a novel oral myeloperoxidase (MPO) inhibitor, in a randomized, single blind, placebo-controlled study, following once daily multiple ascending dosing to steady state in healthy subjects. Target engagement was measured as specific MPO activity in plasma following ex vivo zymosan stimulation of whole blood. Except for generalized maculopapular rash in 4 out of 13 subjects receiving the two highest doses, 15 mg and 45 mg AZD4831, no clinically relevant safety and tolerability findings were observed. AZD4831 was rapidly absorbed and plasma concentrations declined slowly with an elimination half-life of approximately 60 hours. A dose/concentration-effect relationship between MPO inhibition vs. AZD4831 exposure was established with >50 % MPO inhibition in plasma at concentrations in the low nanomolar range. Steady state levels were achieved within 10 days. Taken together the pharmacokinetic profile, the sustained dose/concentration dependent MPO inhibition, and available clinical data support further clinical development of AZD4831 in patients with heart failure with preserved ejection fraction (HFpEF).

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“…Antioxidant enzymes; catalase, CAT 15 , glutathione peroxidase, GPx 16 , glutathione S-transferase, GST 16 , superoxide dismutase, SOD 17 , Myeloperoxidase, MPO 18 activities and concentrations of reduced glutathione, GSH 16 , malondialdehyde, MDA 19 and nitric oxide, NO 20 were determined in serum according to previously described methods.…”

Section: Antioxidant Activity Assaysmentioning

confidence: 99%

Profiling of Phyllanthus Amarus Phytochemical Constituents and Evaluation of Associated Antimalarial Activity and Antioxidant Potential in Experimental Mice

Ezedom,

Onyesom,

Ejiro Awhin

et al. 2023

EIJBPS

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The failing curative ability of antimalarials has prompted an open discussion for the use of antioxidants in combination with antimalarials for effective chemotherapy. This study profiled the phytochemical constituents of Phyllanthus amarus and evaluated their antimalarial and antioxidant activities. Phytochemical screening, antimalarial and acute oral toxicity were determined according to standard procedures. Blood antioxidant activity was assessed by measuring antioxidant enzymes and nitric oxide (NO), concentrations of malarial infected mice treated with P. amarus phytochemicals. Alkaloids, the most abundant phytochemical, demonstrated the highest malarial parasite chemosuppression and greatly improved NO concentration in infected mice. However, flavonoid extract demonstrated the highest antioxidant potential with most significant impact on catalase and malondialdehyde activity. Alkaloid may function as antimalarial agent by inhibiting haem polymerization to hemozoin as judged by its increased effect on NO concentration which bears an reverse relationship with hemozoin.

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Determining myeloperoxidase activity and protein concentration in a single assay: Utility in biomarker and therapeutic studies

Cited by 6 publications

References 9 publications

The potential Anti-Inflammatory and antioxidant activities of Proanthocyanidins in acetic acid–induced ulcerative colitis in rats

The potential Anti-Inflammatory and antioxidant activities of Proanthocyanidins in acetic acid–induced ulcerative colitis in rats

Early Clinical Experience With AZD4831, A Novel Myeloperoxidase Inhibitor, Developed for Patients With Heart Failure With Preserved Ejection Fraction

Profiling of Phyllanthus Amarus Phytochemical Constituents and Evaluation of Associated Antimalarial Activity and Antioxidant Potential in Experimental Mice

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