Blood Pyrrole-Protein Adducts—A Biomarker of Pyrrolizidine Alkaloid-Induced Liver Injury in Humans

Abstract

Pyrrolizidine alkaloids (PAs) induce liver injury (PA-ILI) and is very likely to contribute significantly to drug-induced liver injury (DILI). In this study we used a newly developed ultra-high performance liquid chromatography-triple quadrupole-mass spectrometry (UHPLC-MS)-based method to detect and quantitate blood pyrrole-protein adducts in DILI patients. Among the 46 suspected DILI patients, 15 were identified as PA-ILI by the identification of PA-containing herbs exposed. Blood pyrrole-protein adducts were detected in all PA-ILI patients (100%). These results confirm that PA-ILI is one of the major causes of DILI and that blood pyrrole-protein adducts quantitated by the newly developed UHPLC-MS method can serve as a specific biomarker of PA-ILI.

Expert consensus on the clinical management of pyrrolizidine alkaloid‐induced hepatic sinusoidal obstruction syndrome

“…The findings indicated that serum PPAs had a diagnostic sensitivity of 100.0%, a specificity of 94.1%, a positive predictive value of 95.8%, and a negative predictive value of 100.0%. Blood PPAs assayed by ultra‐high‐performance liquid chromatography‐triple quadrupole‐mass spectrometry can serve as a specific biomarker of PA‐induced liver injury . High serum PPA concentrations indicate a poor prognosis, but few hospitals are equipped able to perform this assay.…”

“…Blood PPAs assayed by ultra-high-performance liquid chromatography-triple quadrupole-mass spectrometry can serve as a specific biomarker of PA-induced liver injury. 59 High serum PPA concentrations indicate a poor prognosis, but few hospitals are equipped able to perform this assay.…”

Pyrrolizidine Alkaloids: Chemistry, Pharmacology, Toxicology and Food Safety

“…In this specific study, the observed HSOS were confirmed to arise from the consumption of a PA-containing plant, Gynura segetum (L.) DC. Another study with PA-induced liver injury led to the conclusion that pyrrole-protein adducts were present in the blood of all the patients, further strengthening the case for their use as biomarkers for this kind of liver injury [ 55 ].…”

Aloe vera: A review of toxicity and adverse clinical effects

“…Herbal dietary supplements and other herbal products have been recognized as the common causes of drug-induced liver injury. [96] A recent report indicates that dietary/herbal supplements are implicated in 19% of drug-induced acute liver failure cases, [97] because consumers often purchase these products online without the supervision of a health care provider and are not aware of drug-herb interactions and appropriate warnings. A total of 1179 English-language, herbal product- related websites (including retail and nonretail websites) were examined and only ~10% of them recommended consultation with a health care professional.…”