Table 1.

Pharmacological/Gene therapy.

Time	Strategies and Description	Species	Ischemic time	Effect	Result
2008 [170]	PPAR-α agonists and adiponectin siRNA	Rat	60 min	MAPK expression and adiponectin accumulation↓	Oxidative and hepatic injury↓
2008 [171]	Allopurinol and apocynin (inhibitor of XOD and NADPH oxidase)	Mice	30 min	Generation of superoxide anions↓	Hepatic injury↓
2008 [172]	Ascorbate (scavenger of ROS)	Rat	30 min	Apoptosis of KCs↓	Hepatic injury↓
2008 [173]	Captopril (Ang 2 blockers)	Rat	60 min	BK generation and PPAR-γ ↑	Hepatic injury↓
2008 [174]	Tetrandine (scavenge ROS and inhibit lipid peroxidation)	Mice	90 min	Neutrophil accumulation, TNF-α and MDA↓ SOD↑	Liver edema and hepatic injury↓
2009 [175] [176]	Mutation of TLR4 or TLR4 knockout	Mice	60 min	Release of pro-inflammatory cytokines and neutrophil infiltration↓	Hepatic injury and damage of LSECs↓
2010 [177]	Carbon monoxide-releasing molecule-2 (CORM-2)	Rat	60 min	Neutrophil infiltration, TNF-α, IL-6, ICAM-1↓ Bcl-2↑	Hepatic injury and levels of apoptosis↓
2010 [178]	Metron factor-1 (MF-1)	Rat	90 min	Oxygen free radicals↓ NO synthesis and survival↑	Hepatic injury and oxidative stress↓
2010 [179]	Sirolimus (immunossupressant drug)	Rat	60 min	Tissue myeloperoxidase and neutrophil infiltration↓	Hepatic injury and liver cell apoptosis↓
2011 [180]	Atorvastatin (HMG-CoA reductase inhibitor)	Mice	60 min	STAR overexpression and mGSH depletion↓	Hepatic injury and oxidative stress↓
2011 [181]	n-3 PUFA (polyunsaturated fatty acid)	Rat	60 min	NF-κB, TNF-α and IL-1β↓	Hepatic injury and oxidative stress↓
2011 [182]	rPSGL-Ig (selectin antagonist)	Human	60min	IL-10↑	Hepatic injury and oxidative stress↓
2012 [183]	ABC294640 (selective inhibitor of sphingosine kinase-2)	Mice	60 min	S1P, neutrophil infiltration, NO synthase, NF-κB and TNF-α↓	Hepatocyte death and hepatic injury↓
2012 [184]	Fasudil (a Rho-kinase inhibitor)	Rat	30 min	HSC activation, endothelin 1 and portal perfusion pressure↓	Hepatic injury and hepatic susceptibility↓
2012 [185]	Nilotinib (tyrosine kinase inhibitor and against JNK and p38 in vitro)	Mice	60 min	Recruitment of inflammatory monocytes, IL-1β, IL-6, MCP-1, MIP-2, JNK and p38 MAPK↓	Hepatocyte apoptosis and hepatic injury↓
2012 [186]	Deletion of FGL2/Fibroleukin (transgenic)	Mice	60 min	Hepatocyte and LSEC protection	Hepatic injury and IRI cascade↓
2013 [187]	RMT1-10 (TIM-1 blocker)	Mice	20 h	Neutrophil and macrophage infiltration/activation, NF-κB and IFN-γ↓ IL-10, IL-22, Bcl-2↑	Hepatic injury and oxidative stress↓
2013 [188]	Simvastatin (immunossupressant drug)	Mice	16 h	Autophagy induction, LSEC injury↓ NO↑	Liver damage, oxidative stress and endothelial dysfunction↓
2014 [189]	rMnSOD (antioxidant)	Mice	20 min	Accumulation of superoxide anion and inflammation↓ NO↑	Hepatic injury and oxidative stress↓
2015 [190] [191]	Knockout of IRF9	Mice	60 min	Serum ALT/AST, immune cell infiltration and levels of inflammatory cytokines ↓	Hepatic injury and hepatocyte apoptosis↓
2016 [192]	Total flavonoids (TFs)	Rat	60 min	MPO, LDH, MDA, IL-6, TNF-α and IL-β↓ SOD and GSH-Px↑	Improve liver histopathology and ultrastructure
2016 [193]	Overactivation of Nrf2-ARE	Mice	60 min	IL-6, IL-1β and levels of 8-isoprostanes↓	Hepatocellular damage, necrosis, apoptosis and oxidative stress↓
2017 [194]	Extracellular vesicles from mesenchymal stem cell (MSC-EV)	Murine	90 min	NF-κB and IL-6↓ Expression of NACHT, LLR and PYD domains-containing protein 12↑	Hepatic caspase 3-positive and apoptotic cells↓
2017 [195]	Inhibition of RAP1/KC/NLRP3 inflammasomes	Mice and human	45 min	Activation of NLRP3 and levels of ALT and ALT↓	Hepatic protection
2018 [196]	Knockout of CARD6	Mice	60 min	NF-κB, JNK, p38 and inflammatory chemokines↓	Hepatic injury and liver cell death↓
2019 [197]	Salicylate acetyl-3-aminoethyl salicylic acid (ac3AESA)	Murine	60 min	Activation of KC, IL-6, TNF-α, IL-β, CXCL2 and CXCL8↓	Hepatic injury and allograft damage↓
2019 [198]	Omeprazole (buffer the acid microenvironment)	Mice and human	60 min	Function of CD4CD25Foxp3 iTregs↑	Hepatic injury↓
2020 [199]	PINK1 (mediate mitophagy)	Mice	60 min	ROS production, NLRP3, and KC-mediated inflammation↓	Hepatic injury and mitochondrial dysfunction↓
2020 [200]	Inhibition of miR-450b-5p	Mice	60 min	CRYAB and M2 polarization↑ NF-κB↓	Hepatic protection
2021 [201]	Overexpression of miR122	Mice and human	60 min	PHD1↓ HIF1α expression↑	Hepatic ischemia tolerance↑
2021 [202]	Inject rhMANF	Mice and human	90 min	Activated ATF4/CHOP and JNK/c-JUN/CHOP pathways↓	UPR injury and hepatocellular damage↓

PPAR-α, peroxisome proliferators-activated receptor-α; PPAR-γ, peroxisome proliferators-activated receptor-γ; TLR4, Toll like receptor 4; TNF-α, tumor necrosis factor α; NLRP3, nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3; IL-1β, interleukin 1β; HMGB1, high-mobility group box 1; IAC, inflammation associated cytokine; IL-1, interleukin 1; IL-6, interleukin 6; IL-10, interleukin 10; IL-22, interleukin 22; NF-κB, nuclear factor κB; ICAM-1, intercellular adhesion molecule-1; Bcl-2/Bcl-x, B cell lymphoma 2/x; MIP-2, macrophage inflammatory protein 2; JNK, N terminal kinase; IFN-γ, interferon γ; ATF4, activating transcription factor 4; CHOP, C/EBP homologous protein; LDH, Lactate dehydrogenase; MDA, malondialdehyde; SOD, superoxide dismutase; GSH-Px, se-dependent enzyme glutathione peroxidase.