Table 1.
Summary of studies investigating the role of sEH in liver diseases. Listed are studies cited in the review, along with details of the experimental design (model, species, and sEHI used) and a brief description of the results and mechanism, if available. Changes in sEH expression or activity are noted in the results column, where available.
| Authors [Ref] | Inhibitor | Disease | Model | Result | Molecular Mechanisms | |
|---|---|---|---|---|---|---|
| In Vivo | In Vitro | |||||
| Iyer et al. [48] | t-AUCB | NAFLD | HFHC Diet, Rat | ↓ Insulin Resistance ↓ Hypertension ↓ Steatosis ↓ Liver Hypertrophy |
↓ Cholesterol ↓ GTT Glucose AUC |
N/A |
| Liu et al. [40] | t-AUCB | NAFLD | HFD, Mouse | ↓ Steatosis ↑ sEH Activity |
↓ Plasma Inflammatory Cytokines ↓ Adipose Macrophage Infiltration |
N/A |
| Bettaieb et al. [41] | TUPS | NAFLD | HFD, Mouse | ↓ Hepatic/Adipose ER Stress ↓ Cell Death, in vitro ↑ Insulin Signaling, in vitro ↑ sEH Protein |
↓ BiP, XBP1, CHOP ↓ Caspase 3, cJUN, JNK, p38 |
EpOMEs and EETs in HepG2 cells: ↑ phospho-IR, phospho-AKT |
| Lopez-Vicario et al. [42] | t-TUCB | NAFLD | HFD, Mouse | ↑ Brown Fat ↑ Hepatic Autophagy ↓ Steatosis ↑ sEH Protein |
↑ IL10, RELMα, CD206, MGL1 ↑ M2 Polarization |
14,15-EET, 19,20-EpDPA, and 17,18-EpETE in Primary Hepatocytes: ↓ Lipid accumulation ↓ phospho-eIF2α, phospho-IRE1α ↑ LC3II:LC3I ratio |
| Sun et al. [43] | PTUPB | NAFLD | HFD, Mouse | ↓ Body/Liver Weight ↓ Liver Injury and Steatosis ↓ Fibrosis ↓ Inflammation ↑ sEH Protein |
↓ NLRP3 Inflammasome Activation ↓ Inflammatory Cytokines ↓ COX2 Expression |
N/A |
| Chen et al. [49] | N/A | NAFLD | HFD, Mouse | ↓ Steatosis ↓ Inflammation ↓ Oxidative Stress |
↓ NFκB ↓ JNK ↑ SOD, GPX |
14,15-EET in HepG2 cells: ↓ NFκB, TNFα, IL1β, IL6 14,15-EET in RAW264.7 cells: ↓ TNFα, IL1β, IL6 |
| Yao et al. [45] | TPPU | NAFLD | HMD, Mouse | ↓ Steatosis ↑ sEH Protein |
↑ Fatty Acid β-Oxidation Genes ↑ PPARα Activation |
sEH Inhibition and 11,12-EET in Primary Hepatocytes: ↑ PPARα Activation |
| Mangels et al. [50] | t-AUCB | Metabolic Syndrome | Mouse | ↓ Cholesterol | ↑ AMPK Activation ↓ SREBP1 ↓ HMG CoA Reductase |
12,13-EpOME in vitro: ↑ phospho-AMPK ↓ HMG CoA Reductase |
| Harris et al. [51] | TPPU | Liver Fibrosis | CCl4, Mouse | ↓ Fibrosis ↓ ER Stress |
↑ Metalloproteases ↓ Col1a2/Col3a1 mRNA ↓ JNK, Caspase 3 |
N/A |
| Zhang et al. [44] | t-TUCB | Liver Fibrosis | CCl4, Rat | ↓ Fibrosis ↓ Portal Hypertension ↓ Inflammation ↓ Oxidative Stress ↑ sEH Protein |
↓ TGFb ↓ Smad ↓ NFkB ↑ Metalloproteases ↑ SOD, GSH |
N/A |
| Deng et al. [52] | t-TUCB | Portal Hypertension | CCl4, Rat | ↓ Portal Pressure ↓ Liver Fibrosis ↓ Liver Endothelial Dysfunction ↑ sEH Protein |
↑ p-eNOS ↑ NO ↓ Caveolin 1 ↓ NFkB |
N/A |
| Fife et al. [53] | AUDA | Sepsis | LPS, Mouse |
n.s. Inflammation ↑ sEH Activity by Lipidome |
↓ iNOS | N/A |
| Chen et al. [38] | TPPU | Sepsis | Cecal Ligation, Puncture, Mouse | ↑ Survival ↓ Organ Damage ↓ Systemic Inflammation |
↑ MAPK Signaling ↑ Macrophage Phagocytosis ↓ Inflammatory Cytokines ↓ ALT/AST, BUN ↓ Bacterial CFU’s |
14,15-EET in vitro: ↓ TNFα, IL1β, IL6 ↑ IL10 |