ArticleScientific reports2015
Unconjugated Bilirubin exerts Pro-Apoptotic Effect on Platelets via p38-MAPK activation.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 71 citations in OpenAlex.
- Development and validation of a nomogram to predict 28-day all-cause mortality in sepsis patients complicated by acute kidney injury.Annals of medicine · 2026Article
- Indirect bilirubin mitigates tubular vacuolization and injury in experimental contrast nephropathy.BMC nephrology · 2026Article
- Hyperbilirubinemia After Redo Valve Surgery: Incidence, Perioperative Risk Factors, and Association with Early Clinical Outcomes.Journal of cardiovascular development and disease · 2026Article
- Bilirubin: a game-changer in alzheimer's therapy? Unveiling its neuroprotective and disease-modifying potential.Metabolic brain disease · 2025Review
- Phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundice.BMC gastroenterology · 2025Article
- Peripheral blood biomarkers as differential diagnostic markers of disease severity in neonates with hyperbilirubinemia.Heliyon · 2025Article
- Bilirubin metabolism in relation to cancer.Frontiers in oncology · 2025Review
- Hematological abnormality and associated factors in newborns with hyperbilirubinemia before and after phototherapy at University of Gondar Comprehensive Specialized Hospital.Scientific reports · 2024Article
- Development and validation of a prediction model for the early occurrence of acute kidney injury in patients with acute pancreatitis.Renal failure · 2023Article
- The Antiproliferative Activity ofMolecules (Basel, Switzerland) · 2023Article
- Development of 1-(4-(Substituted)piperazin-1-yl)-2-((2-((4-methoxybenzyl)thio)pyrimidin-4-yl)oxy)ethanones That Target Poly (ADP-Ribose) Polymerase in Human Breast Cancer Cells.Molecules (Basel, Switzerland) · 2022Article
- Relation Between Unconjugated Bilirubin and Peripheral Biomarkers of Inflammation Derived From Complete Blood Counts in Patients With Acute Stage of Schizophrenia.Frontiers in psychiatry · 2022Article
- Risk factors analysis of hyperbilirubinemia after off-pump coronary artery bypass grafting: a retrospective observational study.Journal of cardiothoracic surgery · 2021Observational
- Challenges of phototherapy for neonatal hyperbilirubinemia (Review).Experimental and therapeutic medicine · 2021Review
- Mitochondrial Function, Fatty Acid Metabolism, and Body Composition in the Hyperbilirubinemic Gunn Rat.Frontiers in pharmacology · 2021Article
- Prediction of Drug-Induced Hyperbilirubinemia by In Vitro Testing.Pharmaceutics · 2020Review
- ASK1 inhibition triggers platelet apoptosisHaematologica · 2020Article
- Sequential Organ Failure Assessment Component Score Prediction of In-hospital Mortality From Sepsis.Journal of intensive care medicine · 2020Article
- Review
- Minocycline protects neurons against glial cells-mediated bilirubin neurotoxicity.Brain research bulletin · 2020Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thrombocytopenia is one of the most frequently observed secondary complications in many pathological conditions including liver diseases, where hyperbilirubinemia is very common. The present study sought to find the cause of thrombocytopenia in unconjugated hyperbilirubinemic conditions. Unconjugated bilirubin (UCB), an end-product of heme catabolism, is known to have pro-oxidative and cytotoxic effects at high serum concentration. We investigated the molecular mechanism underlying the pro-apoptotic effect of UCB on human platelets in vitro, and followed it up with studies in phenylhydrazine-induced hyperbilirubinemic rat model and hyperbilirubinemic human subjects. UCB is indeed found to significantly induce platelet apoptotic events including elevated endogenous reactive oxygen species generation, mitochondrial membrane depolarization, increased intracellular calcium levels, cardiolipin peroxidation and phosphatidylserine externalization (p < 0.001) as evident by FACS analysis. The immunoblots show the elevated levels of cytosolic cytochrome c and caspase activation in UCB-treated platelets. Further, UCB is found to induce mitochondrial ROS generation leading to p38 activation, followed by downstream activation of p53, ultimately resulting in altered expression of Bcl-2 and Bax proteins as evident from immunoblotting. All these parameters conclude that elevated unconjugated bilirubin causes thrombocytopenia by stimulating platelet apoptosis via mitochondrial ROS-induced p38 and p53 activation.
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