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. 2021 Jul 6;12:673562. doi: 10.3389/fimmu.2021.673562

Table 1.

Pharmacological treatment in transplantation field to prevent IR injury.

Indication Drug Study design Results References
Preclinical studies
Renal I/R injury OA Animal model: Rats were administered with OA (12.5, 25 and 50 mg/kg) for 15 consecutive days prior to bilateral renal I/R induction.

  • decreased levels of BUN, sCr, KIM-1 and LDH;

  • decreased levels of MDA, increased activities of superoxide dismutase, catalase and glutathione peroxidase, and increased GSH levels;

  • decreased levels of proinflammatory cytokines and increased of anti-inflammatory cytokine.

 (104)
Leutoline Animal model: male Swiss albino mice were pre-treated with luteolin (100 mg/kg body weight) seven consecutive days before I/R induction.

  • significant reduction in the level of TNF-α, IL-1β, and IL-6;

  • preservation of renal tissue and reduction of apoptotic cells

 (105)
NACand ATOR Animal model: pre-ischemic administration of NAC and/or ATOR (24h before I/R) followed by I/R injury in rats

  • lower MPO and higher GPx activity in NAC, ATOR, and NAC+ATOR group versus I/R group;

  • lower rate of tubular ischemic lesions in NAC+ATOR versus I/R group

 (106)
C5a siRNA Animal model: Mice were injected with 50 μg of C5aR siRNA 2 days before induction of ischemia.

  • reduced BUN and sCr;

  • recovery of renal function;

  • reduced inflammation

 (107)
C3 and Caspase-3 siRNA Animal model: in vivo gene silencing by hydrodynamic injection with C3 and caspase 3 siRNAin mice, before I/R injury.

  • reduced BUN and sCR;

  • recovery of renal function;

  • reduced mortality

 (108)
CD40 siRNA Animal model: injection of siRNA anti-CD40 in rodent warm and cold ischemia models

  • modulation of local and systemic inflammation

 (109)
HDL Animal model:HDL (80 mg/kg, intravenous) was administered to male Wistar rats 30 min before bilateral renal ischemia for 45 min followed by reperfusion for up to 48 h.

  • improved renal function;

  • reduced inflammation;

  • reduced endothelial dysfunction;

  • reduced lipid peroxidation and oxidative stress injury

 (110)
Quercitin Animal model:42 Sprague-Dawley rats were divided into three groups: control, I/R and I/R+quercetin (I/R+Q) . I/R + Q rats were treated with quercetin (50 mg/kg intraperitoneal) 1 h prior to the induction of ischemia.

  • decreased tissue malondialdehyde (MDA) and increased glutathione (GSH) levels;

  • reduction of apoptotic and p53-positive cells, NF-κB and eNOS expression levels

 (111)
Renal I/R injury / EX vivo perfusion /Transplantation Metformin Animal model: metformin preconditioning and postconditioning during ex vivo normothermic machine perfusion (NMP) of rat and porcine kidneys affect I/R injury

  • both metformin preconditioning and postconditioning can be done safely and improved rat and porcine kidney quality.

 (112)
Heparin Animal model: brain-dead porcine donors and murine kidneys during CS

  • amieloration of endothelial function;

  • improved renal function

 (113)
Heparin Animal model: Brain death pigs. Kidneys (matched pairs; n = 6 + 6) were preserved for 20 hours by HMP during which 50 mg heparin conjugate was added to one of the HMP systems (treated group)

  • recovery of renal function;

  • reduced inflammation and preservation of renal parenchyma

 (114)
Quercitin In vitro study: proximal tubular epithelial cells were preincubated for three hours with bioflavonoids and cold stored in University of Wisconsin (UW)- or Euro-Collins (EC)-solution for 20 hours

  • increased cell viability;

  • reduced lipid peroxidation.

 (115)
Quercitin+ Sucrose Animal model: porcine model of renal autologous transplantation. Left kidney grafts were divided in 3 groups: Cold Storage (CS) preservation for 24 hours; CS preservation for 22 hours and hypothermic oxygenated perfusion (HOPE) with CS/MP-UW solution for 2 hours; CS preservation for 22 hours and hypothermic oxygenated perfusion (HOPE) with CS/MP-UW solution with Quercitin and Sucrose added to the solution.

  • amieloration of renal function;

  • reduced oxidative stress and parenchymal damage.

 (116)
Naked Caspase-3 siRNA Animal model: Intravenous injection of 0.9 mg siRNA and right-uninephrectomy; left kidney was autotransplanted for 2 weeks.

  • reduced inflammation;

  • amelioration of renal function.

 (117)
H2S Animal model: bilateral nephrectomy rats underwent renal transplantation with kidneys from donor rats that were flushed with cold solution or cold solution plus 150 μM NaHS (H2S group).

  • reduced renal injury;

  • reduced oxidative stress;

  • reduced Inflammation.

 (118)
H2S Animal model: bilateral nephrectomy rats underwent renal transplantation with kidneys from donor rats that were flushed with cold solution or cold solution plus 150 μM NaHS (H2S group).

  • reduced renal injury;

  • reduced oxidative stress;

  • reduced Inflammation.

 (118)
H2S Animal model: Allogeneic renal transplantation with donor rats that were flushed with cold solution or cold solution plus 150 μM NaHS (H2S group).

  • recovery of mithocondrial function;

  • improved syngraft function.

 (119)
H2S Animal model: Porcine kidneys from Donation after Circulatory Death (DCD)underwent subnormothermic machine perfusion with addition of H2S

  • improvement of organ function.

 (120)
H2S Animal model: porcine DCD kidneys underwent normothermic machine perfusion with addition of H2S

  • controllable hypometabolic state,

  • recovery of renal function.

 (121)
MHC siRNA Animal model: permanent silencing of MHC antigens in transplanted rats.

  • reduced organ immunogenicity;

  • reduced renal damage;

  • reduced inflamamtion.

 (122)
Clinical studies
DGF following deceased donor kidney transplant P53 siRNA Clinical studies: PhaseI-II-III (completed)

  • reduced DGF incidence;

  • favorable recipient outcome.

 https://clinicaltrials.gov/
AKI and (MAKE) following cardiac surgery P53 siRNA Clinical studies: PhaseI-II-III (Phase III ongoing)

  • reduction in the incidence of MAKE composite in the 90 days following cardiac surgery;

  • reduction in the incidence of AKI in the 5 days following cardiac surgery;

  • reduction in the severity and duration of AKI;

  • overall survival.

 https://clinicaltrials.gov/
Deceased donor transplant NAC Clinical study: 74 recipients were randomized to receive NAC 600mg twice a day or placebo.

  • higher mean eGFR throughout the first 90 days and at 1 year;

  • lower risk of DGF.

 (123)

OA, Oleanolic acid; BUN, blood urea nitrogen; sCr,serum creatinine; KIM-1, kidney injury molecule-1; LDH, lactate dehydrogenase; MDA, methane dicarboxylic aldehyde; GSH, glutathione; I/R, Ischemia/reperfusion; HDL, High Density Lipoprotein; NAC, N-Acetylcysteine; ATOR, Atorvastatin; H2S, hydrogen sulfide; MAKE, Major Adverse Kidney Events.