Current Antioxidant Treatments in Organ Transplantation

Table 1

(a) Characteristics of reviewed studies concerning antioxidant treatment for donor. (b) Characteristics of reviewed studies concerning antioxidant treatment for graft. (c) Characteristics of reviewed studies concerning antioxidant treatment for recipient.

(a)

Treatment	Subject	Organ	Model or disease	Effects
Local ischemic preconditioning	Rat [5]	Liver	I/R	NF-κB ↓, MDA ↓, MPO ↓, AST ↓, ALT ↓, Proinflammatory cytokines ↓
	Human [6]	Liver	LiT	Apoptosis ↓, PNF ↓, AST ↑, HIF-1α ↓
	Human [7]	Liver	LiT	No beneficial effect
	Human [8]	Liver	LiR	No beneficial effect
	Human [9]	Liver	LiT	10 min occlusion is optimal
	Rat [10]	Liver	I/R	5/8 min occlusion is optimal
Hydrogen preconditioning	Mice [12]	Lung	MV	W/D ratio ↓, MDA ↓, Egr-1 ↓, TNF-α ↓, IL-1β ↓, CCL2 ↓, apoptosis ↓
	Rat [13]	Lung	LuT	PO2 ↑, PCO2 ↓, ICAM-1 ↓, IL-1β ↓, IL-6 ↓, MDA ↓
	Rat [14]	Liver	I/R	NF-κB ↑, HO-1 ↑, Bcl-2 ↑
	Human [16]	Diabetic	T2DM	LDL ↓, SOD ↑
	Human [17]	Liver	HBV	HBV DNA ↓, ALT ↓, TBiL ↓, SOD ↑, GST ↑
Antioxidant carriers therapy
Immune targeting therapy	Pig [20]	Lung	LuT	Gas exchange ↑, W/D ratio ↓, Edema ↓, MDA ↓
	Human [21]	Cell	HUVECs	VCAM ↑, TNF ↓, IL-1β ↓, LP S ↓
Liposome	Rat [22]	Lung	I/R	PO2 ↑, endothelin-1 ↓, iNOS ↓
	Rat [23]	Liver	LPS-LiI	NPSH ↓, MDA ↓, 4-HNE ↓, ALT ↓, AST ↓, TNF-α ↓
	Rat [24]	Lung	LPS-LuI	NPSH ↓, MDA ↓, 4-HNE ↓, MPO ↓, TNF-α ↓

(b)

Treatment	Subject	Organ	Model or disease	Effects
Machine perfusion	Rat [27]	Liver	HMP	MP at 20°C is optimal, AST ↓, LDH ↓, ATP/ADP ↑, bile production ↑, TNF-α ↓
	Human [28]	Lung	LuT	Subtle beneficial effect
	Rat [29]	Heart	HMP	Apoptosis ↓, MMP-2 ↓, H2O2 ↓, pAkt/Akt ↑
Polymer solutions
Polysol solution	Rat [30]	Liver	SCS	AST ↓, GLDH ↓, PVP ↓, ATP ↑, O2 consumption ↑, bile production ↑, MDA ↓, W/D ratio ↓
	Rat [31]	Liver	PLiT	PVF ↑, ALT ↓, LDH ↓, MDA ↓, VEGF ↑
	Human [32]	Kidney	KT	Acute rejection rate ↑
IGL-1 solution	Pig [33]	Pancreas	PT	Same degree of safety and effectiveness with UW solution
	Human [34]	Kidney	KT	DGF ↓, Cr ↓, apoptosis ↓, Ccr ↑
	Pig [35]	Intestine	IAT	Acute cellular rejection ↓, iNOS ↑, necrosis ↓, apoptosis ↑,
	Human [36]	Liver	LiT	Same degree of safety and effectiveness with UW solution
SCOT solution	Mice [38]	Pancreas	PT	PNF + DGF + allograft survival time ↑
	Human [39]	Kidney	KT	Same degree of safety and effectiveness with UW solution
Gaseous supplements
Hydrogen	Rat [41]	Liver	I/R	ALT ↓, HMGB1 ↓, MDA ↓, TNF-α ↓, IL-6 ↓
	Rat [42]	Kidney	KT	Recipient survival rate ↑, Cr ↓, Ccr ↑, MDA ↓, 8-OHdG ↓
	Rat [43]	Intestine	IAT	MDA ↓, LDH ↓, EGR-1 ↓, IL-6 ↓, iNOS ↓, IL-1β ↓
Nitric oxide	Rat [44]	Liver	LiT	ALT ↓, HA ↓, MDA ↓, eNOS ↑, iNOS ↓, ET-1 ↓, 8-OHdG ↓
	Rat [45]	Lung	LuT	W/D ratio ↓, vascular resistance ↓, cGMP ↑, iNOS ↓, TNF-α ↓
Carbon monoxide	Rat [46]	Kidney	KT	Recipient survival ↑, IL-6 ↓, TNF-α ↓, iNOS ↓, PARP ↑
	Rat [48]	Kidney	KT	ALAS-1 ↑, MDA ↓, IL-6 ↓, TNF-α ↓, Egr-1 ↓, Cox-2 ↓, Ccr ↑
Pharmacologic approaches
Melatonin	Rat [52]	Liver	SCS	AST ↓, ALT ↓, BSP clearance ↑, vascular resistance ↓, eNOS ↑, TNF-α ↓, MDA ↓, HO-1 ↑
Trolox	Pig [54]	Heart	HT	ET-1 ↓, MDA ↓, SOD ↑, TA ↓, LDH ↓, CK ↓, calcium ↓
Doxycycline	Rat [29]	Heart	HMP	Apoptosis ↓, MMP-2 ↓, H2O2 ↓, pAkt/Akt ↑

(c)

Treatment	Subject	Organ	Model or disease	Effects
Ischemic postconditioning
RIPoC	Human [56]	Kidney	KT	Cr ↓, pathology (—), GFR ↑, uNGAL ↓
	Human [57]	Liver	LiT	No beneficial effect
	Human [58]	Kidney	KT	No beneficial effect
LIPoC	Canine [61]	Kidney	KT	MDA ↓, MPO ↓, SOD ↑, apoptosis indices ↓, Cr ↓, BUN ↓, Ccr ↑
	Human [62]	Kidney	KT	Safe but no beneficial effect

ACR: acute cellular rejection; ALAS-1: 5-aminolevulinate synthase; ALT: alanine aminotransferase; AST: aminotransferase; ATP: adenosine triphosphate; BSP: bromosulfophthalein; BUN: blood urea nitrogen; Ccr: creatinine clearance; cGMP: cyclic guanosine monophosphate; Cox-2: cyclooxygenase-2; Cr: creatinine; DGF: delayed graft function; eNOS: endothelial nitric oxide synthase; ET-1: endothelin-1; GFR: glomerular filtration rate; GLDH: glutamate dehydrogenase; GST: glutathione S transferase; HA: hyaluronic acid; HBV: hepatitis B virus; HMP: hypothermic machine perfusion; HSP: heat shock protein; HT: heart transplant; HUVECs: human umbilical endothelial cells; IAT: intestinal allotransplantation; iNOS: inducible nitric oxide synthase; I/R: ischemia and reperfusion; KT: kidney transplantation; LDH: lactate dehydrogenase; LDL: low density lipoprotein; LIPoC: local ischemic postconditioning; LiR: liver resection; LiT: liver transplantation; LPS: lipopolysaccharide; LuT: lung transplantation; MDA: malondialdehyde; MPO: myeloperoxidase; MV: mechanical ventilation; NOS: nitric oxide synthase; NPSH: nonprotein thiols; pAkt: phosphorylated Akt; PARP: poly(ADP-ribose) polymerase; PLiT: partial liver transplantation; PNF: primary nonfunction; PT: pancreas transplantation; PVF: portal venous flow; PVP: portal venous pressure; RIPoC: remote ischemic postconditioning; TA: total antioxidants; TBiL: total bilirubin; TNF: tumor necrosis factor; TLR-4: toll-like receptor-4; T2DM: type 2 diabetes mellitus; SCS: static cold storage; SOD: superoxide dismutase; uNGAL: urine neutrophil gelatinase-associated lipocalin; VEGF: vascular endothelial growth factor; W/D: wet-to-dry; 4-HNE: 4-hydroxyalkenals; 8-OHdG: 8-hydroxy-2-deoxyguanosine.