Beyond Preconditioning: Postconditioning as an Alternative Technique in the Prevention of Liver Ischemia-Reperfusion Injury

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- 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.