Table 2.
Preclinical studies on IP in steatotic livers.
| Author, Year | Animal | Model | Protocol | Ischemia | Findings |
|---|---|---|---|---|---|
| Serafin et al., 2002 [102] | Rat | Partial IRI | 5 min + 10 min 10 min + 10 min 10 min + 15 min |
60 min, warm | 5 + 10 min IP protocol produced better results. Increased survival; reduced ALT; reduced necrosis; lower MDA; increased GSH; increased blood flow. Inhibition of NO production suppressed the protective effects. |
| Selzner et al., 2003 [113] | Mouse | Partial IRI | 10 min + 10 min | 75 min, warm | Reduced AST; reduced necrosis and apoptosis; increased ATP. |
| Serafin et al., 2004 [103] | Rat | Partial IRI | 5 min + 10 min | 60 min, warm | Increased survival; reduced ALT; reduced necrosis; lower MDA; reduced IL-1b and increased IL-10 Inhibition of NO production suppressed the protective effects. |
| Fernandez et al., 2004 [115] | Rat | LT | 5 min + 10 min | 6 h, cold | Reduced AST and ALT; reduced necrosis; reduced MPO; modulation of ROS-generating system and lipid peroxidation. Inhibition of NO production suppressed the protective effects. |
| Carrasco-Chaumel et al., 2005 [72] | Rat | LT | 5 min + 10 min | 6 h, cold | Reduced AST and ALT; reduced necrosis, increased NO production; activation of AMPK signaling. Inhibition of NO production suppressed the protective effects. |
| Niemann et al., 2005 [117] | Rat | LT | 10 min + 10 min | 4 h, cold | Increased survival; increased ATP; lower lactate |
| Koti et al., 2005 [108] | Rat | Partial IRI | 5 min + 10 min | 45 min, warm | Reduced AST and ALT; increased ATP; increased oxygenation and microcirculation |
| Massip-Salcedo et al., 2006 [109] | Rat | Partial IRI | 5 min + 10 min | 60 min, warm | Reduced AST and ALT; reduced necrosis; increased HO-1; downregulation of MAPK pathway. Inhibition of NO production and/or HO-1 suppressed the protective effects. |
| Saidi et al., 2007 [112] | Rat | Partial IRI | 10 min + 15 min | 75 min, warm | Reduced AST; reduced IL-6; reduced necrosis. |
| Massip-Salcedo et al., 2008 [110] | Rat | Partial IRI | 5 min + 10 min | 60 min, warm | Reduced ALT; reduced necrosis; lower MDA; reduced IL-1b; PPAR-α upregulation; adiponectin downregulation; downregulation of MAPK pathway. Inhibition of PPAR-α suppressed the protective effects. |
| Casillas-Ramirez et al., 2008 [104] | Rat | Partial IRI | 5 min + 10 min | 60 min, warm | Reduced ALT; reduced IL-1, reduced necrosis; reduced angiotensin II. ACE-inhibitors produced same benefits. |
| Rolo et al., 2009 [111] | Rat | Partial IRI | 5 min + 10 min | 90 min, warm | Reduced AST and ALT; reduced membrane mitochondrial depolarization; increased ATP; reduced MPT induction |
| Hafez et al., 2010 [105] | Rabbit | Partial IRI | 5 min + 10 min | 60 min, warm | Reduced AST and ALT; increased oxygenation and microcirculation, improved bile quality |
| Casillas-Ramirez et al., 2011 [114] | Rat | LT | 5 min + 10 min | 6 h, cold | Reduced AST and ALT; reduced necrosis. Increased AMPK activation; PPAR-γ downregulation. Inhibition of AMPK suppressed the protective effects. |
| Jiang et al., 2013 [106] | Rat | Partial IRI | 5 min + 10 min 8 min + 10 min 10 min + 10 min 15 min + 10 min |
30 min, warm | 5 + 10 min and 8 + 10 min IP protocols produced better results. Reduced AST, ALT and LDH; increased NO production, reduced MPO; lower MDA; |
| Pantazi et al., 2014 [107] | Rat | Partial IRI | 5 min + 10 min | 60 min, warm | Reduced AST; reduced necrosis and apoptosis; increased NO production; activation of AMPK signaling. Increased levels of sirtuin 1. Inhibition of sirtuin 1 suppressed the protective effects. |
| Chu et al., 2015 [118] | Rat | SCS | 10 min + 10 min | 24 h, cold | Reduced complex I injury. Protective effects only with mild steatosis, not with moderate/severe steatosis. |
| Jimenez-Castro et al., 2015 [116] |
Rat | LT | 5 min + 10 min | 6 h, cold | Increased survival; reduced ALT and AST; increased NO production, reduced MPO; lower MDA; PPAR-α upregulation; PPAR-γ downregulation. Inhibition of NO production suppressed the protective effects. |
Abbreviations: AMPK, adenosine monophosphate-activated protein kinase; GSH, glutathione; HO-1, heme oxygenase 1; IP, ischemic preconditioning; LT, liver transplantation; MDA, malondialdehyde; MPO, myeloperoxidase; MPT, mitochondrial permeability transition; PPAR-α, proliferator-activated receptor-α; PPAR-γ, proliferator-activated receptor-γ.