Table 1.

Roles of nitric oxide, endothelial nitric oxide synthase and inducible nitric oxide synthase in pharmacological protection against hepatic ischemia reperfusion injury

Pretreatment	NO/iNOS/eNOS levels	Animals	Experimental cells	Mechanism	Liver cell necrosis and liver damage	Ref.
L-arginine and HIRI	NO↑	Male Sprague-Dawley rats	Hepatocytes	O2-↓, NO2-/NO3- concentration↑	↓	[6]
L-NAME and HIRI	NO↓	Male Sprague-Dawley rats	Liver cells	NO2-/NO3- concentration↓	↑	[7]
Human serum albumin↑	NO↑	Rats underwent HIRI	Liver parenchyma	Man-rHSAs↑	↓	[8]
SNAP and HIRI	NO↑	-	Vein endothelial cells	ICAM, TNF-α, NF-κB, p38, ERK, JNK, p53, caspase-3↓	↓	[9,10]
Nitrite and hypoxia/reoxygenation	NO↑	Trachemys Acripta elegans	Various cell types	Cytochrome oxidase, oxygen radical↓	↓	[13]
L-arginine and HIRI	NO↑	-	Liver cells	sGC, cGMP, PKG, PI3K, V-ATPase↑, intracellular Na+, H+↓	↓	[5]
L-arginine and HIRI	NO↑	Rats	Liver cells	TNF-α, IL-1β↓	↓	[14,15]
HIRI	eNOS,NO↑	-	Bovine aortic endothelial cells and COS-7cells	Intracellular Na+, H+, PKC, Ca2+↑	↓	[16,17]
rHuEPO and HIRI	NO↑	Adult male Sprague-Dawley rats	Liver cells	PI3K/Akt/eNOS pathway	↓	[18]
Institut Georges Lopez-1 and HIRI	eNOS↑	Adult male SD rats	Liver cells	Akt,AMPK↑	↓	[19]
Adiponectin and HIRI	eNOS↑	Adult male Wistar rats	Hepatocytes	AMPK/eNOS pathway	↓	[20]
Heparin cofactor II and ischemia	eNOS↑	Male heterozygote HCII-deficient mice and male littermate WT mice	Vascular endothelial cell	AMPK/eNOS signaling pathway	↓	[21]
Trimetazidine, IGL-1, and HIRI	eNOS,NO↑	Isolated perfused rats liver model	Steatotic and non-steatotic livers cells	HIF-1α, heme-oxygenase-1↑	↓	[22]
Knockdown of AK139328 and HIRI	eNOS↑	Mice	Liver cells	p-eNOS, p-Akt, PGSK-3↑,macrophage infiltration, NF-κB↓	↓	[23]
Ad-eNOS and HIRI	eNOS↑	Male inbred C57BL/6 lean mice	Liver cells	ATP↓, bax↑	↑	[24]
Riboflavin and HIRI	eNOS,iNOS,NO↓	Mice	Liver	GSH↑	↓	[25]
Rosmarinic acid and HIRI	eNOS,iNOS,NO↓	Rats	Liver	eNOS excessive expression↓ NF-κB activity, TNF-α and IL-1β gene expression↓	↓	[26]
Alpha lipoic acid and HIRI	iNOS,NO↓	Male Wistar strain rats	Hepatocytes	iNOS mRNA stability↓	↓	[31]

-: No data; Man-rHSAs: Mannosylated-HSA mutants; HIRI: Hepatic ischemia reperfusion injury; IGL-1: Institut georges lopez-1; SNAP: S-nitroso-N-acetylpenicillamine; ICAM: Intercellular adhesion molecule; Akt: Protein kinase B; AMPK: Adenosine monophosphate-activated protein kinase; TNF-α: Tumor necrosis factor-α; NF-κB: Nuclear factor-κ-gene binding; ERK: Extracellular regulated protein kinase; JNK: c-Jun N-terminal kinase; PI3K: Phosphoinositide 3-kinase; V-ATPase: Vacuolar H⁺-ATPase; rHuEPO: Recombinant human erythropoietin; HIF-1α: Hypoxia inducible factor 1α; PGSK-3: Phosphorylated glycogen synthase kinase 3; eNOS: Endothelial nitric oxide synthase; iNOS: Inducible nitric oxide synthase.