Pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome: Pathogenesis, clinical manifestations, diagnosis, treatment, and outcomes

Figure 1 Pathogenesis of pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome. A: Oral PAs are transported into the liver, metabolites bind with glutathione, resulting in detoxification, or combine with protein to generate PPAs; B: In HSECs, PPAs cause depolymerization of F-actin and release of MMP-9, which damages HSECs; C: Injured HSECs round up, MMP-9 triggers degradation of extracellular matrix, then gaps between HSECs appear, blood cells penetrate the gaps into the space of Disse, and sinusoidal lining cells obstruct the sinusoidal flow, resulting in postsinusoidal portal hypertension. PAs: Pyrrolizidine alkaloids; GSH: Glutathione; PPAs: Protein-pyrrole adducts; HSECs: Hepatic sinusoidal endothelial cells; MMP-9: Matrix metalloproteinase-9; ECM: Extracellular matrix; DHPAs: Dehydropyrrolizidine alkaloids; DHR: Dehydroretronecine; HSOS: Hepatic sinusoidal obstruction syndrome.