Pyrrolizidine Alkaloids: Potential Role in the Etiology of Cancers, Pulmonary Hypertension, Congenital Anomalies, and Liver Disease

Abstract

Large outbreaks of acute food-related poisoning, characterized by hepatic sinusoidal obstruction syndrome, hemorrhagic necrosis, and rapid liver failure, occur on a regular basis in some countries. They are caused by 1,2-dehydropyrrolizidine alkaloids contaminating locally grown grain. Similar acute poisoning can also result from deliberate or accidental consumption of 1,2-dehydropyrrolizidine alkaloid-containing herbal medicines, teas, and spices. In recent years, it has been confirmed that there is also significant, low-level dietary exposure to 1,2-dehydropyrrolizidine alkaloids in many countries due to consumption of common foods such as honey, milk, eggs, salads, and meat. The level of 1,2-dehydropyrrolizidine alkaloids in these foods is generally too low and too intermittent to cause acute toxicity. However, these alkaloids are genotoxic and can cause slowly developing chronic diseases such as pulmonary arterial hypertension, cancers, cirrhosis, and congenital anomalies, conditions unlikely to be easily linked with dietary exposure to 1,2-dehydropyrrolizidine alkaloids, especially if clinicians are unaware that such dietary exposure is occurring. This Perspective provides a comprehensive review of the acute and chronic toxicity of 1,2-dehydropyrrolizidine alkaloids and their potential to initiate certain chronic diseases, and suggests some associative considerations or indicators to assist in recognizing specific cases of diseases that may have resulted from dietary exposure to these hazardous natural substances. If it can be established that low-level dietary exposure to 1,2-dehydropyrrolizidine alkaloids is a significant cause of some of these costly and debilitating diseases, then this should lead to initiatives to reduce the level of these alkaloids in the food chain.

Determination of Pyrrolizidine Alkaloids in Honey with Sensitive Gas Chromatography-Mass Spectrometry Method

“…However, the chronic, insidious poisoning caused by intermittent, low-level intake of PAs is more difficult to associate with adverse health effects, especially when they become apparent years after consumption (Boppré 2011). The chronic disease that can be initiated by the low-level dietary exposure to 1,2-unsaturated PAs includes a wide range of cancers, progressive liver disorders leading to cirrhosis, congenital anomalies, and pulmonary arterial hypertension (Edgar et al 2015).…”

Transfer of pyrrolizidine alkaloids from various herbs to eggs and meat in laying hens

“…Although the transfer and levels in animal-derived products seem relatively low, exposure via such products may still be relevant. This is due to the fact that various PAs were shown to contain genotoxic and carcinogenic properties, meaning that even intake of low levels by humans may result in adverse effects (Fu et al 2004;EFSA 2011;Edgar et al 2015). The common policy is to reduce the presence of genotoxic carcinogens in our food as much as possible.…”

Synthetic Strategies towards the Azabicyclo[3.3.0]-Octane Core of Natural Pyrrolizidine Alkaloids. An Overview

“…43 More than half of the known PAs are connected with hepato-toxic, carcinogenic and genotoxic effects on humans. [44][45][46][47][48][49] Poisoning occurs via consumption of either contaminated food or medicinal plants in the form of dietary supplements or teas. In general, PAs with unsaturated pyrrolizidine core are hepato-toxic, whereas those with saturated core are considered non-toxic.…”

“…Depending on the ring substitution and saturation, the pyrrolizidine alkaloids show various biological effects including valuable anti-bacterial, anti-viral, anti-tumor, antidiabetic, or anti-inflammatory properties. [1][2][3] These small bicyclic ring systems of pharmacological relevance, containing stereocenters, are valuable but challenging targets for synthetic chemists. This explains the enduring interest in the development of efficient preparation of various PAs over the years.…”