ArticleActa pharmaceutica Sinica. B2021
The key role of gut-liver axis in pyrrolizidine alkaloid-induced hepatotoxicity and enterotoxicity.
Article in Acta pharmaceutica Sinica. B, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- Red blood cell damage defines the etiology of hepatic sinusoidal obstruction syndrome induced by pyrrolizidine alkaloids.Acta pharmaceutica Sinica. B · 2026Article
- Taoling Yuyang Decoction alleviates DSS-induced ulcerative colitis in mice by regulating gut microbiota -metabolite axis and restore intestinal barrier function.Frontiers in microbiology · 2026Article
- [Rifaximin curative effect and mechanism on monocrotaline-induced hepatic sinusoidal obstruction syndrome in mice].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Article
- Targeted inhibition of Gus-expressingActa pharmaceutica Sinica. B · 2024Article
- Functional metabolomics characterizes the contribution of farnesoid X receptor in pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome.Archives of toxicology · 2024Article
- Pyrrolizidine Alkaloids-Pros and Cons for Pharmaceutical and Medical Applications.International journal of molecular sciences · 2023Review
- Gut microbiota-based pharmacokinetic-pharmacodynamic study and molecular mechanism of specnuezhenide in the treatment of colorectal cancer targeting carboxylesterase.Journal of pharmaceutical analysis · 2023Article
- Article
- Integrative Metabolomics and Proteomics Detected Hepatotoxicity in Mice Associated with Alkaloids fromToxins · 2022Article
- Structure-Dependent Toxicokinetics of Selected Pyrrolizidine Alkaloids In Vitro.International journal of molecular sciences · 2022Article
- Article
- Gut microbiota-derived metabolites in inflammatory diseases based on targeted metabolomics.Frontiers in pharmacology · 2022Article
- Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pyrrolizidine alkaloids (PAs) are the most common phytotoxins with documented human hepatotoxicity. PAs require metabolic activation by cytochromes P450 to generate toxic intermediates which bind to proteins and form protein adducts, thereby causing cytotoxicity. This study investigated the role of the gut-liver axis in PA intoxication and the underlying mechanisms. We exposed mice to retrorsine (RTS), a representative PA, and for the first time found RTS-induced intestinal epithelium damage and disruption to intestinal barrier function. Using mice with tissue-selective ablation of P450 activity, we found that hepatic P450s, but not intestinal P450s, were essential for PA bioactivation. Besides, in RTS-exposed, bile duct-cannulated rats, we found the liver-derived reactive PA metabolites were transported by bile into the intestine to exert enterotoxicity. The impact of gut-derived pathogenic factors in RTS-induced hepatotoxicity was further studied in mice with dextran sulfate sodium (DSS)-induced chronic colitis. DSS treatment increased the hepatic endotoxin level and depleted hepatic reduced glutathione, thereby suppressing the PA detoxification pathway. Compared to RTS-exposed normal mice, the colitic mice displayed more severe RTS-induced hepatic vasculature damage, fibrosis, and steatosis. Overall, our findings provide the first mode-of-action evidence of PA-induced enterotoxicity and highlight the importance of gut barrier function in PA-induced liver injury.
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