A toxicoproteomic study was performed on liver of rats treated with retrorsine (RTS), a representative hepatotoxic pyrrolizidine alkaloid at a toxic dose (140 mg/kg) known to cause severe acute hepatotoxicity. By comparing current data with our previous findings in mild liver lesions of rats treated with a lower dose of RTS, seven proteins and three toxicity pathways of vascular endothelial cell death, which was further verified by observed sinusoidal endothelial cell losses, were found uniquely associated with retrorsine-induced hepatotoxicity. This toxicoproteomic study of acute pyrrolizidine alkaloid intoxication lays a foundation for future investigation to delineate molecular mechanisms of pyrrolizidine alkaloid-induced hepatotoxicity.
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http://dx.doi.org/10.1080/10590501.2018.1450186 | DOI Listing |
Lipophilicity and blood partitioning are important determinants for predicting toxicokinetics using physiologically-based toxicokinetic (PBTK) modeling. In this study, the logarithm of the -octanol:water partition coefficient (log) and the blood-to-plasma concentration ratio ( ) were for the first time experimentally determined for the pyrrolizidine alkaloids (PAs) intermedine, lasiocarpine, monocrotaline, retrorsine and their -oxides (PANOs). Validated assays for log (miniaturized shake-flask method) and (LC-MS/MS-based depletion assay) determination were compared to an ensemble of models.
View Article and Find Full Text PDFFront Pharmacol
January 2025
Department of Pharmacy, College of Medicine and Health Sciences, Debre Markos University, Debre Markos, Ethiopia.
is a genus of over 50 species that are commonly used in primary care in several countries. This study seeks to inspire researchers to quickly discover and isolate the key active metabolites found in taxa, thereby promoting the development of novel, safe, and effective therapies for a variety of illnesses. To this end, we performed a thorough search of English-language publications from PubMed, Scopus, ScienceDirect, Web of Science, Google Scholar, and ResearchGate.
View Article and Find Full Text PDFJ Pharm Biomed Anal
January 2025
ADSI, Austrian Drug Screening Institute GmbH, Innrain 66a, Innsbruck 6020, Austria.
The aim of this work was to develop and validate a rapid dispersive-solid-phase extraction method for the quantification of pyrrolizidine alkaloids (PA) from plant extracts. The method was focused on the significant removal of the intricate matrix to ensure good sensitivity for the subsequent instrumental analysis of PA. This was achieved by employing nano-zirconium silicate (NZS) as a dispersive-SPE sorbent.
View Article and Find Full Text PDFRespir Res
January 2025
Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), 13 Hangkong Road, Wuhan, 430030, China.
This study introduced a novel dual fixation method for the pulmonary vasculature and lung tissue in pulmonary hypertension (PH) rats, addressing the limitations of traditional fixation methods that failed to accurately preserve the in vivo status of pulmonary vascular morphology. The modified method involved a dual fixation process, combining individualized ventilation support and vascular perfusion to simulate the respiratory motion, pulmonary artery pressure and right ventricular output of the rat under in vivo conditions. Utilizing a monocrotaline-induced PH rat model, this study compared the dual fixation with the traditional immersion fixation, focusing on the quantitative assessment of alveolar expansion degree, capillary patency, endothelial cell quantity and wall thickness of pulmonary vein and artery.
View Article and Find Full Text PDFJ Ethnopharmacol
January 2025
Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China. Electronic address:
Ethnopharmacological Relevance: Emilia sonchifolia is a very widely used traditional Chinese medicine, with the efficacy of heat-clearing, detoxicating, dissipating blood stasis, reducing swelling and relieving pain. As a widely used traditional miao herb, Emilia sonchifolia is often used to treat upper respiratory tract infections, oral ulcer, pneumonia, mastitis, enteritis, bacillum, urinary tract infection, sores, eczema, falls and injuries, etc. In fact, many cases of liver injury caused by Emilia sonchifolia have been reported clinically.
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