Melatonin on Elevated Liver Enzymes During Statins Treatment
The Effects of Melatonin on Elevated Liver Enzymes During Statins Treatment
Introduction Statins are widely used in the treatment and prevention of lipid metabolism disorders. They are generally well tolerated but not devoid of side effects. These include, among others, muscular symptoms, arthritis, headaches, gynecomastia. Myositis and rhabdomyolysis associated with increased activity of creatinine kinase and serum creatinine levels are rare but serious adverse events of statin therapy.
- The risk of these complications is increased in elderly patients with chronic diseases and in alcohol abusers.
- Furthermore, statins cause hepatotoxic effect which is observed in several percent of treated patients, usually in the first weeks of the therapy . Most frequently it is manifested by asymptomatic increase in the level of aspartate and alanine aminotransferase.
- This is usually a temporary increase, but in some patients the level of these enzymes exceeds 3 times the normal limit, which is a matter of concern. In such cases, patients expect the decision to discontinue the treatment or to administer hepatoprotective drugs.
- Acetylcholine, sylibinin, phospholipids and other drugs used for this purpose are not always effective. Therefore, there is still search for alternative drugs for the protection of liver.
In own study melatonin was used for this purpose because previous experimental studies had demonstrated that it protected liver against harmful effects of many toxic agents as well as the consequences of ischemia-reperfusion model.
The liver is an organ in which there comes to intensive metabolic and detoxification processes. In their course large amounts of reactive oxygen species are generated and they exert a toxic effect on hepatocytes.
A complex antioxidant system – in which metabolized there melatonin (pineal and from other sources) is an important part – prevents that.
The main melatonin metabolic pathway in the liver is through hydroxylation pathway at the C-6 position by 6-hydroxylase and P450 cytochromes (CYP1A1, CYP1A2, CYP2P19, CYP1B1 isozymes). The 6-hydroxymelatonin, formed in this process, is conjugated with sulphate and glucuronide to 6-hydroxymelatonin sulphate or glucuronide. In this process melatonin and its metabolites exert high antioxidant activity.
An alternative metabolic pathway includes melatonin oxidation to N-acetyl-formyl-5- methoxykynuramine (AFMK) and N-acetyl-5-methoxykynuramine (AMK). The kynurenine pathway of melatonin metabolism leads to formation of a series of free radical scavengers.
Furthermore, melatonin decreases the production of proinflammatory cytokines and inhibits hepatic fibrogenesis. Owing to its multidirectional action in liver, apoptosis and necrosis decrease, the integrity is protected and regeneration is improved.

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E01C0729-48 | BlueGene | 1 plate of 48 wells | EUR 520 |
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SCA518Hu-1x96wellstestplate | Cloud-Clone | 1x96-wells test plate | EUR 746.8 |
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4-SCA518Hu | Cloud-Clone |
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4-SEA518Hu | Cloud-Clone |
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Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Human Ferritin (FE) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids with no significant corss-reactivity with analogues from other species. |
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The aim of this study was to assess the usefulness of melatonin in counteracting the adverse hepatic events from statins.
Material and Methods Patients and Data Collection The research program included 30 subjects, aged 47-68 years, 41 women and 23 men. All women were I the postpostmenopausal period. Recruitment and diagnostic tests were conducted in the Department of Gastroenterology, Medical University of Lodz and Outpatient Consulting Clinic “Gastro” in Lodz.
The research study was performed in the years 2012-2016. Therapeutic Procedures After inclusion into the study, all patients were recommended the same balanced diet with limited animal fats and simple carbohydrates of caloric content of 1600 kcal. At the same time, they were recommended to continue the treatment with the same statin at a daily dose of 20 mg.
The patients were randomly allocated into two groups. Group I (n=30) was recommended to take statin together with melatonin (LEK-AM, Poland) at a dose of 2×5 mg, at 7:00 a.m. and 9:00 p.m. In Group II (n=30) patients took statin with placebo (LEK-AM, Poland) at the same dose and time of the day.
Follow-up laboratory tests (AST, ALT, GGT, ALP, cholesterol and triglycerides) were evaluated after 2,4 and 6 months of treatment.
Ethical procedures A written consent was obtained from the patients and the Bioethics Committee of the Medical University in Lodz approved the study protocol (RNN/45/12/KB).
Tests were conducted in accordance with the Declaration of Helsinki and with the principles of Good Clinical Practice.
Statistical analysis All parameters were checked for normality using the Shapiro-Wilk test. Wilcoxon’s rank sum test was used for the comparison of basal treatment differences between each liver enzyme level.
Comparison of parameters in four time series was calculated using ANOVA Friedman test. Mann-Whitney U test was used for nonparametric data to perform the comparison between groups. Calculation were made using Statistical 9.1 Microsoft Co. software, and statistical significance was established at p< 0,05.
Acknowledgments This work was supported by the grant from the Polish Ministry of Science and Higher Education No: NN 402 54 37/40.
Competing Interests The authors declare that they have no competing interests.
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E02A2159-96 | BlueGene | 1 plate of 96 wells | EUR 685 |
Description: A competitive for quantitative measurement of Rat Angiotensin Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Anti-Angiotensin Converting Enzyme 1 (6A4) |
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YF-MA12650 | Abfrontier | 100 ug | EUR 363 |
Description: Mouse monoclonal to Angiotensin Converting Enzyme 1 |
![]() Anti-Angiotensin Converting Enzyme 1 (4B10) |
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YF-MA12651 | Abfrontier | 100 ug | EUR 363 |
Description: Mouse monoclonal to Angiotensin Converting Enzyme 1 |
![]() Mouse Angiotensin Converting Enzyme ELISA kit |
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E03A2159-192T | BlueGene | 192 tests | EUR 1270 |
Description: A competitive for quantitative measurement of Mouse Angiotensin Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Mouse Angiotensin Converting Enzyme ELISA kit |
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E03A2159-48 | BlueGene | 1 plate of 48 wells | EUR 520 |
Description: A competitive for quantitative measurement of Mouse Angiotensin Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Mouse Angiotensin Converting Enzyme ELISA kit |
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E03A2159-96 | BlueGene | 1 plate of 96 wells | EUR 685 |
Description: A competitive for quantitative measurement of Mouse Angiotensin Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Rabbit Angiotensin Converting Enzyme ELISA kit |
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E04A2159-192T | BlueGene | 192 tests | EUR 1270 |
Description: A competitive for quantitative measurement of Rabbit Angiotensin Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Rabbit Angiotensin Converting Enzyme ELISA kit |
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E04A2159-48 | BlueGene | 1 plate of 48 wells | EUR 520 |
Description: A competitive for quantitative measurement of Rabbit Angiotensin Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Rabbit Angiotensin Converting Enzyme ELISA kit |
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E04A2159-96 | BlueGene | 1 plate of 96 wells | EUR 685 |
Description: A competitive for quantitative measurement of Rabbit Angiotensin Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Recombinant Angiotensin I Converting Enzyme (ACE) |
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4-RPA004Hu01 | Cloud-Clone |
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Description: Recombinant Human Angiotensin I Converting Enzyme expressed in: E.coli |
![]() Recombinant Angiotensin I Converting Enzyme (ACE) |
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4-RPA004Hu02 | Cloud-Clone |
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Description: Recombinant Human Angiotensin I Converting Enzyme expressed in: E.coli |
![]() Recombinant Angiotensin I Converting Enzyme (ACE) |
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4-RPA004Mu01 | Cloud-Clone |
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Description: Recombinant Mouse Angiotensin I Converting Enzyme expressed in: E.coli |
![]() Recombinant Angiotensin I Converting Enzyme (ACE) |
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4-RPA004Mu02 | Cloud-Clone |
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Description: Recombinant Mouse Angiotensin I Converting Enzyme expressed in: E.coli |
![]() Recombinant Angiotensin I Converting Enzyme (ACE) |
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4-RPA004Mu03 | Cloud-Clone |
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Description: Recombinant Mouse Angiotensin I Converting Enzyme expressed in: E.coli |
![]() Recombinant Angiotensin I Converting Enzyme (ACE) |
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4-RPA004Po01 | Cloud-Clone |
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Description: Recombinant Pig Angiotensin I Converting Enzyme expressed in: E.coli |
![]() Recombinant Angiotensin I Converting Enzyme (ACE) |
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4-RPA004Rb01 | Cloud-Clone |
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Description: Recombinant Rabbit Angiotensin I Converting Enzyme expressed in: E.coli |
![]() Monkey Angiotensin Converting Enzyme ELISA kit |
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E09A2159-192T | BlueGene | 192 tests | EUR 1270 |
Description: A competitive for quantitative measurement of Monkey Angiotensin Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Monkey Angiotensin Converting Enzyme ELISA kit |
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E09A2159-48 | BlueGene | 1 plate of 48 wells | EUR 520 |
Description: A competitive for quantitative measurement of Monkey Angiotensin Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Monkey Angiotensin Converting Enzyme ELISA kit |
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E09A2159-96 | BlueGene | 1 plate of 96 wells | EUR 685 |
Description: A competitive for quantitative measurement of Monkey Angiotensin Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Pig Angiotensin Converting Enzyme ELISA kit |
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E07A2159-192T | BlueGene | 192 tests | EUR 1270 |
Description: A competitive for quantitative measurement of Porcine Angiotensin Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Pig Angiotensin Converting Enzyme ELISA kit |
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E07A2159-48 | BlueGene | 1 plate of 48 wells | EUR 520 |
Description: A competitive for quantitative measurement of Porcine Angiotensin Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Pig Angiotensin Converting Enzyme ELISA kit |
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E07A2159-96 | BlueGene | 1 plate of 96 wells | EUR 685 |
Description: A competitive for quantitative measurement of Porcine Angiotensin Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Dog Angiotensin Converting Enzyme ELISA kit |
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E08A2159-192T | BlueGene | 192 tests | EUR 1270 |
Description: A competitive for quantitative measurement of Canine Angiotensin Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Dog Angiotensin Converting Enzyme ELISA kit |
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E08A2159-48 | BlueGene | 1 plate of 48 wells | EUR 520 |
Description: A competitive for quantitative measurement of Canine Angiotensin Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Dog Angiotensin Converting Enzyme ELISA kit |
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E08A2159-96 | BlueGene | 1 plate of 96 wells | EUR 685 |
Description: A competitive for quantitative measurement of Canine Angiotensin Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Goat Angiotensin Converting Enzyme ELISA kit |
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E06A2159-192T | BlueGene | 192 tests | EUR 1270 |
Description: A competitive for quantitative measurement of Goat Angiotensin Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Goat Angiotensin Converting Enzyme ELISA kit |
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E06A2159-48 | BlueGene | 1 plate of 48 wells | EUR 520 |
Description: A competitive for quantitative measurement of Goat Angiotensin Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Goat Angiotensin Converting Enzyme ELISA kit |
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E06A2159-96 | BlueGene | 1 plate of 96 wells | EUR 685 |
Description: A competitive for quantitative measurement of Goat Angiotensin Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Active Angiotensin I Converting Enzyme (ACE) |
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4-APA004Hu02 | Cloud-Clone |
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Description: Recombinant Human Angiotensin I Converting Enzyme expressed in: Available from E.coli, Yeast, Baculovirus and Mammalian cells |
![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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20-abx128667 | Abbexa |
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![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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20-abx129494 | Abbexa |
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![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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20-abx129607 | Abbexa |
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![]() Angiotensin-Converting Enzyme 2 (ACE2) Antibody |
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20-abx313823 | Abbexa |
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![]() Angiotensin-Converting Enzyme (CD143) Antibody (FITC) |
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abx413654-01mg | Abbexa | 0.1 mg | EUR 578 |
![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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20-abx270178 | Abbexa |
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![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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20-abx270179 | Abbexa |
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![]() Angiotensin I-Converting Enzyme Substrate Peptide |
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20-abx265670 | Abbexa |
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![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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20-abx241080 | Abbexa |
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![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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20-abx241081 | Abbexa |
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![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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abx159297-100ul | Abbexa | 100 ul | EUR 467 |
![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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20-abx241727 | Abbexa |
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![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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20-abx214211 | Abbexa |
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![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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20-abx175391 | Abbexa |
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![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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20-abx175393 | Abbexa |
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![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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20-abx171229 | Abbexa |
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![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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20-abx171230 | Abbexa |
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![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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20-abx171231 | Abbexa |
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![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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20-abx171232 | Abbexa |
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![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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20-abx171233 | Abbexa |
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![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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abx230080-100ug | Abbexa | 100 ug | EUR 481 |
![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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20-abx328371 | Abbexa |
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![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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20-abx325361 | Abbexa |
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![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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20-abx103103 | Abbexa |
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![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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20-abx103104 | Abbexa |
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![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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20-abx103105 | Abbexa |
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![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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abx037354-100ug | Abbexa | 100 ug | EUR 391 |
![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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abx140499-01mg | Abbexa | 0.1 mg | EUR 356 |
![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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20-abx007362 | Abbexa |
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![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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abx025482-100ul | Abbexa | 100 ul | EUR 523 |
![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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abx033685-400ul | Abbexa | 400 ul | EUR 523 |
![]() Angiotensin I Converting Enzyme (ACE) Antibody |
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abx033685-80l | Abbexa | 80 µl | EUR 286 |
![]() Monoclonal Angiotensin Converting Enzyme 1 Antibody |
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APG01871G | Leading Biology | 0.1ml | EUR 484 |
Description: A Monoclonal antibody against Human Angiotensin Converting Enzyme 1. The antibodies are raised in Mouse. This antibody is applicable in WB |
![]() Anti-Angiotensin Converting Enzyme 1 antibody |
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STJ99092 | St John's Laboratory | 200 µl | EUR 197 |
Description: Mouse monoclonal to Angiotensin Converting Enzyme 1. |
![]() Angiotensin Converting Enzyme 2 Conjugated Antibody |
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C49072 | SAB | 100ul | EUR 397 |
![]() Angiotensin I-Converting Enzyme (ACE) Inactivator |
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N-1360.0250 | Bachem | 250.0mg | EUR 576 |
Description: Sum Formula: C21H21N3O4; CAS# [144085-32-5] |
![]() Angiotensin I-Converting Enzyme (ACE) Inactivator |
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N-1360.1000 | Bachem | 1.0g | EUR 1663 |
Description: Sum Formula: C21H21N3O4; CAS# [144085-32-5] |
![]() Rabbit Angiotensin converting enzyme,ACE ELISA Kit |
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ELA-E0004Rb | Lifescience Market | 96 Tests | EUR 928 |
![]() Rat Angiotensin converting enzyme,ACE ELISA Kit |
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CN-01619R1 | ChemNorm | 96T | EUR 447 |
![]() Rat Angiotensin converting enzyme,ACE ELISA Kit |
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CN-01619R2 | ChemNorm | 48T | EUR 296 |
![]() Mouse Angiotensin converting enzyme,ACE ELISA Kit |
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CN-02491M1 | ChemNorm | 96T | EUR 449 |
![]() Mouse Angiotensin converting enzyme,ACE ELISA Kit |
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CN-02491M2 | ChemNorm | 48T | EUR 299 |
![]() Human Angiotensin converting enzyme,ACE ELISA Kit |
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CN-03160H1 | ChemNorm | 96T | EUR 438 |
![]() Human Angiotensin converting enzyme,ACE ELISA Kit |
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CN-03160H2 | ChemNorm | 48T | EUR 289 |
![]() Human Angiotensin I Converting Enzyme ELISA kit |
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E01A0498-192T | BlueGene | 192 tests | EUR 1270 |
Description: A sandwich ELISA for quantitative measurement of Human Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Human Angiotensin I Converting Enzyme ELISA kit |
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E01A0498-48 | BlueGene | 1 plate of 48 wells | EUR 520 |
Description: A sandwich ELISA for quantitative measurement of Human Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Human Angiotensin I Converting Enzyme ELISA kit |
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E01A0498-96 | BlueGene | 1 plate of 96 wells | EUR 685 |
Description: A sandwich ELISA for quantitative measurement of Human Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Human Angiotensin I Converting Enzyme ELISA kit |
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E01A0707-192T | BlueGene | 192 tests | EUR 1270 |
Description: A competitive ELISA for quantitative measurement of Human Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Human Angiotensin I Converting Enzyme ELISA kit |
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E01A0707-48 | BlueGene | 1 plate of 48 wells | EUR 520 |
Description: A competitive ELISA for quantitative measurement of Human Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Human Angiotensin I Converting Enzyme ELISA kit |
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E01A0707-96 | BlueGene | 1 plate of 96 wells | EUR 685 |
Description: A competitive ELISA for quantitative measurement of Human Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Human Angiotensin II Converting Enzyme ELISA kit |
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E01A0709-192T | BlueGene | 192 tests | EUR 1270 |
Description: A Sandwich ELISA for quantitative measurement of Human Angiotensin II Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Human Angiotensin II Converting Enzyme ELISA kit |
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E01A0709-48 | BlueGene | 1 plate of 48 wells | EUR 520 |
Description: A Sandwich ELISA for quantitative measurement of Human Angiotensin II Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Human Angiotensin II Converting Enzyme ELISA kit |
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E01A0709-96 | BlueGene | 1 plate of 96 wells | EUR 685 |
Description: A Sandwich ELISA for quantitative measurement of Human Angiotensin II Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
![]() Rat Angiotensin I Converting Enzyme ELISA kit |
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E02A0498-192T | BlueGene | 192 tests | EUR 1270 |
Description: A sandwich ELISA for quantitative measurement of Rat Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |