Protective Effect Of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) On Renal Ischemia-reperfusion Injury

Aim:Renal ischemia-reperfusion injury(IRI)is a common consequence of acute kidney injury(AKI).nicotinamide adenine dinucleotide phosphate(NADPH)that came from pentose phosphate pathway(PPP),which is the main component for the proper functioning of some essential redox and antioxidant defense systems.The goal of this study was to analyze the NADPH’s protective function in the renal ischemia-reperfusion injury.Methoeds:The IRI models were attained by a midline laparotomy method for the surgery having an incision with clamping on both sides of renal pedicles for about 40 min to induce the kidney’s ischemia.The oxygen and glucose were removed from the human kidney epithelial(HK-2)cells then the re-oxygenation(OGD/R)followed to imitate the IRI.We tested the levels of BUN,Scr,Renal index to definite the protective effects of NADPH on renal ischemia reperfusion injury.We also explored the possible mechanism of its effects.Results:1.the NADPH safeguarded the kidneys from histological and functional damage,significantly preventing a potential increase of the blood urea nitrogen(BUN)(22.837±9.504 vs 8.310±1.424mmol/L P<0.01;22.837 vs 11.630±5.160mmol/L P<0.05);and the creatinine(Cr)levels(82.887±58.230 vs 23.561±8.462μmol/L P<0.01;82.887±58.230 vs 33.234±31.343μmol/L P<0.0).2.PAS staining indicated kidney tissues from the IRI group showed overt swelling in the renal tubular cells,increased inflammatory cells and coagulating necrosis;furthermore,the disappearance of the brush border and vacuole degeneration were also observed.The mice receiving 1 or 5mg/kg NADPH both showed a marked reduction in renal histopathology injuries3.The studies showed that the NADPH increased the levels of glutathione(GSH)(4.367±0.962 vs 6.160±1.386μmol/g prot P<0.01;4.367±0.962 vs 5.645±1.047μmol/g prot P<0.05);and reduced the levels of malondialdehyde(MDA)(1.167±0.104 vs 0.948±0.107nmol/mg prot P<0.001;1.167 vs 1.030±0.115nmol/mg prot P<0.001)in kidney,compared with sham group.4.The results noted that NADPH treatment reversed the Bcl-2 and Bax expression compared with IRI group.Consistently,IRI increased the Cleaved-Caspase3 level,which was also reduced by NADPH.Moreover,compared with the sham group,IκB-α expression in the model group was decreased and the Cox-2 level was increased.Both of these phenotypes were reversed by NADPH treatment.5.In vitro,NADPH significantly increased cell viability following OGD/R and decreased the ROS level in cells compared with untreated group.NADPH could inhabit the nuclear localization of P65.Conclusion:1.NADPH treatment may have protective effects on renal IRI.Compared with the sham-operated group,the level of serum Cr and BUN in the IRI group were elevated.2.NADPH has a protective influence on HK-2 cells from oxygen-glucose deprivation/reperfusion-induced injury.3.NADPH Attenuates Oxidative Stress In Vivo and In Vitro.4.NADPH Blocks Apoptosis In Vivo and In Vitro.5.NADPH Suppresses NF-κB Activity In Vivo and In Vitro.