Hepatotoxicity Evaluation on Foodborne Pyrrolizidine Alkaloids

Abstract

Recently aristolochic acids from plants of genera Aristolochia and Asarum raised public concerns in their implication in liver cancer. However, pyrrolizidine alkaloids (PAs) (another group of hepatotoxic phytotoxins) induce hepatic injury more overwhelming, because increasing evidence suggests that many plant-derived foodstuffs are frequently contaminated with PAs. Dietary exposure to PAs is potentially to induce chronic liver diseases such as liver fibrosis and cancer. To date, over 10,000 human poisoning cases associated with PA intake have been reported. The present study aims to investigate the contamination of PAs in retail honey in China and evaluate the progressive toxicity via a long-term exposure to PAs. Among 375 honey samples purchased from 21 regions in Mainland China, Hong Kong, Macau, and Taiwan, 218 samples (58%) were detected to contain toxic PAs ranging over 0.04–288 μg/kg. Using the modified metric for estimating the toxicity, over one third of the honey samples tested may potentially provoke health problems via their daily intake, according to the available exposure thresholds of PAs. Further toxicity evaluation was performed using male mice with or without alcoholic liver disease (ALD) and inflammatory bowel disease (IBD). Mice were orally administrated with retrorsine (RTS), a typical hepatotoxic PA, for 14 consecutive weeks. Progressive pathological lesions, including persistent inflammation, vascular hyperplasia, fibrosis and steatosis, were found in RTS-treated mice and significantly exacerbated in mice with ALD or IBD. Moreover, 10 months after the termination of RTS treatment, mixed type of liver tumors combined with late stage of steatotic hepatitis and cirrhosis developed in the liver of RTS-treated mice. In conclusion, our findings unraveled that 1) there is a high prevalence of PA contamination in Chinese retail honey; and 2) long-term intake of PAs may give rise to liver cirrhosis and/or tumor. The study warrants the monitoring of toxic PAs in foods and the follow-up diagnosis of PA-associated progressive liver injury. Support or Funding Information Supported by Research Grants Council of Hong Kong Special Administrative Region (GRF Project No. 14110714 and 14111816), CUHK One-off Funding for Joint Lab/Research Collaboration (Project Code: 3132968) and CUHK Direct Grant (Project No. 4054302) and School of Biomedical Sciences–Seed Fund for Joint Establishments. Graphical abstract This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.