Abstract
<b>Abstract ID 53998</b> <b>Poster Board 458</b> Pyrrolizidine alkaloids (PAs) are widely distributed natural toxins. Aside from their extensively-studied hepatotoxicity, our previous report demonstrated that pneumotoxicity was commonly induced by retronecine and otonecine types PAs. Monocrotaline (MCT) as a widely used agent to induce pulmonary arterial hypertension has been frequently investigated for its toxicity on pulmonary vessels. Besides vascular damage, PA-induced airway damage is poorly defined. Here we aimed to systematically investigate PA-induced chronic obstructive pulmonary disease. In the present study, rats were orally administered with a single dose of MCT (0.2 mmol/kg) and sacrificed 4 weeks after exposure. Histological examinations including various staining techniques were applied to evaluate the pathological changes in airways and alveoli induced by MCT. The results revealed that, apart from pulmonary vascular pathology, MCT also induced alveolar inflammation (lymphocytes, neutrophils, and macrophages accumulation and infiltration into alveolar space), alveolar damage (alveolar type II pneumocyte hyperplasia, emphysema, and edema), and airway remodelling (goblet cell metaplasia, and loss of adherens adjunction) in rats. In conclusion, we present the first systematical characterization of MCT-induced obstructive lung diseases in rats, which is initiated by endothelial damage with inflammatory responses as a crucial mediator. Our findings have both clinical and public health implications. Till now, PA poisoning cases in humans are almost manifested by liver injury, mostly due to the ingestion of PA-contaminated grains or PA-containing herbal medicines. Considering that, i) different PAs commonly induce pulmonary toxicity, and ii) humans are frequently exposed to PAs via ingestion of PA-containing herbal medicines or PA-contaminated foods, it is extrapolated that PA exposure might serve as a contributor to human obstructive lung disease incidence, and further investigations are warranted. [The present study was supported by General Research Fund (Project Nos. 14160817, 14107719 and 14106318) from Research Grants Council of Hong Kong Special Administrative Region and Direct Grant (Project No. 4054656) from The Chinese University of Hong Kong.]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.