ArticleScientific reports2017
Biliverdin Reductase inhibitors did not improve severe unconjugated hyperbilirubinemia in vivo.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
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- Portosystemic shunt placement reveals blood signatures for the development of hepatic encephalopathy through mass spectrometry.Nature communications · 2023Article
- Metabolic Functions of Biliverdin IXβ Reductase in Redox-Regulated Hematopoietic Cell Fate.Antioxidants (Basel, Switzerland) · 2023Review
- Long-Term Effects of Biliverdin Reductase a Deficiency inAntioxidants (Basel, Switzerland) · 2021Article
- A Transcriptomic Approach to the Metabolism of Tetrapyrrolic Photosensitizers in a Marine Annelid.Molecules (Basel, Switzerland) · 2021Article
- Induction of cell apoptosis by biliverdin reductase inhibitor in MCF-7 and MDA-MB-468 breast cancer cell lines: Experimental and in silico studies.EXCLI journal · 2021Article
- A QuantitativeMolecular therapy. Methods & clinical development · 2020Article
- Prediction of Drug-Induced Hyperbilirubinemia by In Vitro Testing.Pharmaceutics · 2020Review
- Heme-Derived Metabolic Signals Dictate Immune Responses.Frontiers in immunology · 2020Review
- Experimental models assessing bilirubin neurotoxicity.Pediatric research · 2020Review
- A Novel Fluorescence-Based Assay for the Measurement of Biliverdin Reductase Activity.Reactive oxygen species (Apex, N.C.) · 2018Article
- Modulating the Biliverdin Reductase (BVR)/ERK1/2 Axis to Attenuate Oxidative Stress in Rat Arterial Rings.Iranian journal of pharmaceutical research : IJPRArticle
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We aimed to identify potent biliverdin reductase (BVRA) inhibitors as a novel concept for the treatment of severe unconjugated hyperbilirubinemia. 1280 FDA-approved compounds were screened in vitro for their ability to inhibit human and rat BVRA activity and 26 compounds were identified as BVRA inhibitors. Montelukast and Disulfiram were selected as potentially clinically applicable drugs and tested to reduce serum unconjugated bilirubin (UCB) levels in the Ugt1a1-deficient rat, a model for chronic unconjugated hyperbilirubinemia. Oral administration of Disulfiram was toxic in the Ugt1a1-deficient rat (weight loss, transaminase elevation). Oral Montelukast administration led to low serum concentrations and did not alter serum UCB levels. Intraperitoneal injections of Montelukast resulted in concentrations up to 110 μmol/L in serum and 400 μmol/L in the liver. Still, serum UCB levels remained unaltered. This first study on biliverdin reductase inhibition as a novel concept for treatment of unconjugated hyperbilirubinemia identified putative in vitro BVRA inhibitors. Montelukast, the clinically most suitable inhibitor, did not result in reduction of serum UCB in the Ugt1a1-deficient rat. The proposed treatment strategy will not result in amelioration of severe unconjugated hyperbilirubinemia in humans without the identification or development of more potent BVRA inhibitors.
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