ReviewInternational journal of molecular sciences2021
Metabolic Toxification of 1,2-Unsaturated Pyrrolizidine Alkaloids Causes Human Hepatic Sinusoidal Obstruction Syndrome: The Update.
Review in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Cocoa-Based Plant Matrices in Glucose Metabolism: Bioactive Compounds and Redox Signaling.Antioxidants (Basel, Switzerland) · 2026Review
- Pyrrolizidine Alkaloid-Induced Hepatotoxicity: A Narrative Review on Molecular Mechanisms and Detoxification Strategies.Antioxidants (Basel, Switzerland) · 2026Review
- Hepatic Sinusoidal Obstruction Syndrome Induced by Pyrrolizidine Alkaloids fromMolecules (Basel, Switzerland) · 2026Review
- Khat-associated Autoimmune Hepatitis: A Review with RUCAM Analysis.Journal of clinical and translational hepatology · 2025Review
- Drug-induced hepatic sinusoidal obstruction syndrome: current advances and future perspectives.Archives of toxicology · 2025Review
- Review
- Copper, Iron, Cadmium, and Arsenic, All Generated in the Universe: Elucidating Their Environmental Impact Risk on Human Health Including Clinical Liver Injury.International journal of molecular sciences · 2024Review
- Wilson Disease: Copper-Mediated Cuproptosis, Iron-Related Ferroptosis, and Clinical Highlights, with Comprehensive and Critical Analysis Update.International journal of molecular sciences · 2024Review
- OCT1-dependent uptake of structurally diverse pyrrolizidine alkaloids in human liver cells is crucial for their genotoxic and cytotoxic effects.Archives of toxicology · 2023Article
- Rifaximin Prevents Intestinal Barrier Dysfunction and Alleviates Liver Injury in MCT-induced HSOS Mice.Current medical science · 2023Article
- Assessment of Toxic Pyrrolizidine and Tropane Alkaloids in Herbal Teas and Culinary Herbs Using LC-Q-ToF/MS.Foods (Basel, Switzerland) · 2023Article
- New Insights into Herb-Induced Liver Injury.Antioxidants & redox signaling · 2023Review
- Molecular Idiosyncratic Toxicology of Drugs in the Human Liver Compared with Animals: Basic Considerations.International journal of molecular sciences · 2023Review
- Pyrrolizidine alkaloids and health risk of three Boraginaceae used in TCM.Frontiers in pharmacology · 2023Article
- Treatment of Drug-Induced Liver Injury.Biomedicines · 2022Review
- Pyrrolizidine Alkaloid Extraction and Analysis: Recent Updates.Foods (Basel, Switzerland) · 2022Review
- Aluminum, Arsenic, Beryllium, Cadmium, Chromium, Cobalt, Copper, Iron, Lead, Mercury, Molybdenum, Nickel, Platinum, Thallium, Titanium, Vanadium, and Zinc: Molecular Aspects in Experimental Liver Injury.International journal of molecular sciences · 2022Review
- Ethnobotany, Phytochemistry, Biological, and Nutritional Properties of GenusPlants (Basel, Switzerland) · 2022Review
- Investigation ofFrontiers in microbiology · 2022Article
- Liquorice Extract and 18β-Glycyrrhetinic Acid Protect Against Experimental Pyrrolizidine Alkaloid-Induced Hepatotoxicity in Rats Through Inhibiting Cytochrome P450-Mediated Metabolic Activation.Frontiers in pharmacology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Saturated and unsaturated pyrrolizidine alkaloids (PAs) are present in more than 6000 plant species growing in countries all over the world. They have a typical heterocyclic structure in common, but differ in their potential toxicity, depending on the presence or absence of a double bond between C1 and C2. Fortunately, most plants contain saturated PAs without this double bond and are therefore not toxic for consumption by humans or animals. In a minority of plants, however, PAs with this double bond between C1 and C2 exhibit strong hepatotoxic, genotoxic, cytotoxic, neurotoxic, and tumorigenic potentials. If consumed in error and in large emouns, plants with 1,2-unsaturated PAs induce metabolic breaking-off of the double bonds of the unsaturated PAs, generating PA radicals that may trigger severe liver injury through a process involving microsomal P450 (CYP), with preference of its isoforms CYP 2A6, CYP 3A4, and CYP 3A5. This toxifying CYP-dependent conversion occurs primarily in the endoplasmic reticulum of the hepatocytes equivalent to the microsomal fraction. Toxified PAs injure the protein membranes of hepatocytes, and after passing their plasma membranes, more so the liver sinusoidal endothelial cells (LSECs), leading to life-threatening hepatic sinusoidal obstruction syndrome (HSOS). This injury is easily diagnosed by blood pyrrolizidine protein adducts, which are perfect diagnostic biomarkers, supporting causality evaluation using the updated RUCAM (Roussel Uclaf Causality Assessment Method). HSOS is clinically characterized by weight gain due to fluid accumulation (ascites, pleural effusion, and edema), and may lead to acute liver failure, liver transplantation, or death. In conclusion, plant-derived PAs with a double bond between C1 and C2 are potentially hepatotoxic after metabolic removal of the double bond, and may cause PA-HSOS with a potential lethal outcome, even if PA consumption is stopped.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.