Table 2.
Summary of outcome of studies on pharmacological postconditioning of the liver.
| Study group | Year | Species | Hepatic ischemia | Ischemia time | Reperfusion time | Pharmacological inducer of postconditioning | Parameters assessed | Outcome of postconditioning (postconditioning versus control) | Proposed mechanism |
|---|---|---|---|---|---|---|---|---|---|
| Guo et al. [63] | 2011 | Mouse | Warm and partial | 60 min | 2/4/12 h | Ginsenoside Rb1 | ALT, MDA, SOD, NO, e-NOS, TNF-α, ICAM-1, HIF-1α, PI3K-Akt, and histopathology | (i) ↓ALT, MDA, TNF-α, and ICAM-1 (ii) ↑SOD, NO, and e-NOS (iii) ↑HIF-1α and PI3K-Akt (iv) Lower scores of cytoplasmic vacuolization, sinusoidal congestion, and hepatocyte necrosis |
Suppression of proinflammatory mediators and adhesion molecules, e-NOS mediated NO production through PI3K-Akt, and upregulation of HIF-1α through NO |
|
| |||||||||
| Dal Ponte et al. [58] | 2011 | Rat | Hepatocyte culture and cold storage (in vitro)/warm partial ischemia (in vivo) | 24 h cold ischemia/60 min warm ischemia | 120 min | A2A receptor agonist | Hepatocyte viability, ALT, PI3K-Akt, and histopathology | (i) ↓ALT (ii) ↑hepatocyte viability and PI3K-Akt (iii) Fewer necrotic areas on histological examination |
Activation of PI3K-Akt pathway |
|
| |||||||||
| Beck-Schimmer et al. [56] | 2012 | Man | Warm and total | At least 30 min | Not standard | Sevoflurane | AST, ALT (peak postop levels), postop complications, and length of hospital stay | (i) ↓AST (ii) ALT not different from control (iii) ↓incidence of complications and shorter hospital stay |
Not addressed |
|
| |||||||||
| Shawky et al. [64] | 2012 | Rat | Warm and partial | 45 min | 120 min | Recombinant human erythropoietin | AST, ALT, caspase-9 activity, Fas ligand expression, antiapoptotic Bcl-xL/apoptotic Bax ratio, and histopathology | (i) ↓AST and ALT (ii) No change in Fas ligand expression (iii) Improved histology scores (iv) Preconditioning with rhEPO more effective than postconditioning in the reduction of caspase-9 activity and the increase of antiapoptotic Bcl-xL/apoptotic Bax ratio |
Modulation of apoptosis cascade |
|
| |||||||||
| Tian et al. [53] | 2013 | Rat | Warm and partial | 60 min | 120 min | Diazoxide | AST, ALT, pkc-ε, Bcl-2, cytochrome c, and caspase-3 | (i) ↓AST and ALT (ii) ↑pkc-ε and Bcl-2 (iii) ↓cytochrome c and caspase-3 |
Upregulation of pkc-ε, opening of mito-KATP channels, and inhibition of the apoptotic pathway |
|
| |||||||||
| Toyoda et al. [52] | 2014 | Rat | Warm and partial | 60 min | 5 h | Milrinone | AST, ALT, LDH, histopathology, and apoptotic score | (i) ↓AST, ALT, and LDH (ii) Improved histology scores and lower apoptotic rate |
Activation of PI3K-Akt pathway and upregulation |
ALT: alanine aminotransferase; MDA: malondialdehyde; SOD: superoxide dismutase; NO: nitric oxide; e-NOS: endothelial NO synthase; TNF-α: tumor necrosis factor-alpha; ICAM-1: intercellular adhesion molecule-1; HIF-1α: hypoxia inducible factor 1-alpha; PI3K-Akt: phosphatidylinositol 3-kinase; AST: aspartate aminotransferase; pkc-ε: protein kinase c-epsilon; LDH: lactate dehydrogenase.