Decreased expression of sirtuin 3 protein correlates with early stage chronic renal allograft dysfunction in a rat kidney model

Abstract

Chronic renal allograft dysfunction (CRAD) is the primary factor affecting the long-term survival of patients who have undergone renal transplantation. Oxidative stress and inflammation serve an important role in the pathological damage caused by CRAD in the early post-transplantation phase. Previous studies have demonstrated that sirtuin 3 (sirt3) protects cells from oxidative stress and inflammation. A model of renal orthotopic transplantation was established in the current study and kidney samples were harvested from the rats 12 weeks following surgery. Compared with the control groups, there were significantly increased levels of serum creatinine, blood urea nitrogen and 24 h urinary protein in the allograft group (P<0.05). Pathological examinations indicated mononuclear cell infiltration and intimal proliferation in the allograft group, which had a higher Banff score compared with the control groups. There were increased levels of malondialdehyde, decreased sirt3 protein expression and decreased superoxide dismutase enzyme activity in the allograft group compared with the control groups (P<0.05). In addition, there was a negative correlation between the expression of sirt3 and 24 h urinary protein excretion, serum creatinine levels, tubulointerstitial mononuclear cell infiltration, smooth muscle cell migration in the vascular wall and Banff scores. Thus, sirt3 may serve an important protective role in the early stage of CRAD.

Inhibition of Glycogen Synthase Kinase 3β Alleviates Chronic Renal Allograft Dysfunction in Rats

“…51 In our previous studies, oxidative stress was also demonstrated by increased levels of MDA, 8-isoprostane, oxidized low-density lipoprotein, and 8-hydroxy-2′-deoxyguanosine; meanwhile, inadequate antioxidant defense was illustrated via decreased levels of the antioxidant enzymes total SOD, catalase, glutathione peroxidase, glutathione reductase, and γ-glutamylcysteine synthetase in CRAD rats. 9,52 Besides, it has been reported that syndecan-1 shedding with GM6001 played renoprotective roles against ischemia-reperfusion injury by phosphorylation of GSK-3β. 53 Consistent with these results, our present study found that the kidney of CRAD rats has increased levels of MDA and decreased levels of SOD.…”

Pharmacotherapy against Oxidative Stress in Chronic Kidney Disease: Promising Small Molecule Natural Products Targeting Nrf2-HO-1 Signaling

“…F344 rat kidneys were orthotopically transplanted into Lewis rats. At 12 weeks following surgery, the kidney expressed a higher level of MDA and lower levels of SOD activity, with increased levels of pathological damaging biomarkers such as serum creatinine levels and the infiltration of tubulointerstitial mononuclear cells, indicating the role of OS in CRAD [62].…”

Amelioration of Renal Injury by Resveratrol in a Rat Renal Transplantation Model via Activation of the SIRT1/NF-κB Signaling Pathway

“…F334-to-LEW orthotopic renal transplantation was performed as previously described under a surgical ASX-2 microscope (Shanghai Anxin Optical Instrument Manufacture Co., Ltd., Shanghai, China) [ 19 ]. Rats were anesthetized with 3% sodium pentobarbital (30 mg·kg −1 ) via intraperitoneal injection.…”