Pyrrole-protein adducts, a mechanism-based biomarker of pyrrolizidine alkaloid induced hepatotoxicity
Refereed conference paper presented and published in conference proceedings



摘要Pyrrolizidine alkaloids (PAs) are among the most hepatotoxic phytotoxins present in about 3% of the flowering plants. Ingestion of PAs causes hepatic sinusoidal obstruction syndrome (HSOS), characterized by primary sinusoidal endothelial cell damage. The hepatic cytochrome P450-mediated metabolic activation of PAs leading to the formation of pyrrole-protein adducts has been considered the major pathway in initiating PA-induced liver injury (PA-ILI). Our previous studies provided evidence to support that pyrrole-protein adducts can potentially serve as a biomarker of PA exposure and PA-ILI. The present study aimed to 1) investigate the correlation between the level of pyrrole-protein adducts formed from the metabolism of different PAs and their hepatotoxic potency; and 2) characterize the binding specificity, dose-response, and elimination kinetics of blood pyrrole-protein adducts in rats. Two PA-containing herbs Crotalaria sessiliflora (containing senecionine and seneciphylline) and Gynura segetum (containing monocrotaline), and a representative toxic PA (monocrotaline) were used for the study. We observed that there was a good correlation between the level of dose-dependent hepatotoxicity (determined by the elevation of serum ALT) and the formation of pyrrole-protein adducts in the liver of rats treated with different PAs. There was also a good correlation between the hepatic and the blood on the level of pyrrole-protein adduct formation. The results indicated that pyrrole-protein adducts were formed dose-dependently in all the monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and residual protein fractions, with the highest level of pyrrole-protein adducts in Hb fraction. The elimination half-lives of pyrrole-protein adducts in rat Hb, plasma proteins, albumin, and residual proteins were determined to be 12.08 ± 1.06, 2.81 ± 0.08, 2.54 ± 0.11, and 2.93 ± 0.04 days, respectively. These findings suggest that pyrrole-Hb adduct is a potential minimal invasive biomarker of PA exposure and PA-ILI.
著者Jiang MA, Mi LI, Yang YE, Peter P. FU, Ge LIN
會議名稱Experimental Biology Meeting 2018
會議地點San Diego, California
期次Supp 1

上次更新時間 2021-21-09 於 00:13