Metabolic Toxification of 1,2-Unsaturated Pyrrolizidine Alkaloids Causes Human Hepatic Sinusoidal Obstruction Syndrome: The Update.

Saturated and unsaturated pyrrolizidine alkaloids (PAs) are present in more than 6000 plant species growing in countries all over the world. They have a typical heterocyclic structure in common, but differ in their potential toxicity, depending on the presence or absence of a double bond between C1 and C2. Fortunately, most plants contain saturated PAs without this double bond and are therefore not toxic for consumption by humans or animals. In a minority of plants, however, PAs with this double bond between C1 and C2 exhibit strong hepatotoxic, genotoxic, cytotoxic, neurotoxic, and tumorigenic potentials. If consumed in error and in large emouns, plants with 1,2-unsaturated PAs induce metabolic breaking-off of the double bonds of the unsaturated PAs, generating PA radicals that may trigger severe liver injury through a process involving microsomal P450 (CYP), with preference of its isoforms CYP 2A6, CYP 3A4, and CYP 3A5. This toxifying CYP-dependent conversion occurs primarily in the endoplasmic reticulum of the hepatocytes equivalent to the microsomal fraction. Toxified PAs injure the protein membranes of hepatocytes, and after passing their plasma membranes, more so the liver sinusoidal endothelial cells (LSECs), leading to life-threatening hepatic sinusoidal obstruction syndrome (HSOS). This injury is easily diagnosed by blood pyrrolizidine protein adducts, which are perfect diagnostic biomarkers, supporting causality evaluation using the updated RUCAM (Roussel Uclaf Causality Assessment Method). HSOS is clinically characterized by weight gain due to fluid accumulation (ascites, pleural effusion, and edema), and may lead to acute liver failure, liver transplantation, or death. In conclusion, plant-derived PAs with a double bond between C1 and C2 are potentially hepatotoxic after metabolic removal of the double bond, and may cause PA-HSOS with a potential lethal outcome, even if PA consumption is stopped.

Heavy Metal Accumulation in Water, Soil, and Plants of Municipal Solid Waste Landfill in Vientiane, Laos.

The municipal solid waste (MSW) landfill in Vientiane, Laos, which receives > 300 tons of waste daily, of which approximately 50% is organic matter, has caused serious environmental problems. This study was conducted to investigate the accumulated levels of heavy metals (HMs) (cadmium (Cd), chromium (Cr), copper (Cu), nickel (Ni), lead (Pb), and zinc (Zn)) in water (surface and groundwater), soil, and plants between dry and wet seasons according to the standards of the Agreement on the National Environmental Standards of Laos (ANESs), Dutch Pollutant Standards (DPSs), and the World Health Organization (WHO), respectively. Although no impact of pollution on the surface water was observed, the levels of Cr and Pb in the groundwater significantly exceeded the basics of ANESs and WHO in both seasons. The pollution caused by Cd and Cu reached the eco-toxicological risk level in the landfill soils and its vicinity. The vegetable Ipomoea aquatica, which is consumed by the nearby villagers, was seriously contaminated by Cr, Pb, Cu, and Zn, as the accumulation of these toxic metals was elevated to much greater levels as compared to the WHO standards. For the grass Pennisetum purpureum (elephant grass), the quantities of HMs in all plant parts were extreme, perhaps due to the deeper growth of its rhizome than I. aquatica. This study is the first to warn of serious HM pollution occurring in the water, soil, and plants in the MSW landfill of Vientiane, Laos, which requires urgent phytoremediation. The indication of what sources from the MSW principally cause the pollution of HMs is needed to help reduce the toxicological risks on Lao residents and the environment in Vientiane as well.