File:Fphar-13-1037814-g003.jpg

English: Schematic diagram of the molecular mechanisms of RFP-induced liver injury. Inhibition of FXR/SHP pathway promotes bile synthesis and activates PKC/ERK/JNK/p38 pathway to inhibit bile transport leading to cholestasis. Regulation of PERK/ATF4/CHOP and HMGB1/RAGE pathways to generate endoplasmic reticulum stress. RFP promotes hepatic fatty acid synthesis and absorption, respectively, by regulating hepatic fatty acid-related factors, resulting in the accumulation of hepatic lipids. Notes: RFP, rifampicin; FXR: farnesoid X receptor; SHP: small heterodimer partner; CYP7A1, cholesterol 7α hydroxylase; PKC, protein kinase C; ERK, extracellular signal-regulated kinases; JNK, c-jun N-terminal kinase; p38, p38 mitogen-activated protein kinases; AP-2, adaptin 2; GP78: E3 ubiquitin ligase; MRP2: multidrug resistance-associated protein 2; GRP78, glucose-regulated protein 78; HMGB1, high mobility group box 1 protein; RAGE: receptor for advanced glycation end products; PERK, protein kinase R-like endoplasmic reticulum kinase; ATF4, activating transcription factor 4; CHOP, C/EBP homologous protein; ERS, endoplasmic reticulum stress; NF-κB, nuclear factor-κB; FAS, fatty acid synthase; ACC, acetyl CoA carboxylase; SCD-1: stearoyl CoA desaturase 1; PXR: pregnane X receptor; PPAR-γ, peroxisome proliferator-activated receptor-γ; APOC3, apolipoprotein C-III, ACBP: acyl-CoA-binding protein; ThA, 3-ketoacyl-CoA thiolase A; ThB, 3-ketoacyl-CoA thiolase B; PLIN2, perilipin-2.