Oleanolic Acid Improves the Symptom of Renal Ischemia Reperfusion Injury via the PI3K/AKT Pathway

Purpose: The aim of this study was to investigate the therapeutic effect of oleanolic acid (OA) on the renal ischemia reperfusion injury (RIRI) and the possible mechanism. Methods: The RIRI model was successfully established in rats. OA, LY294002 (a PI3K inhibitor), and OA combined with LY294002 were dosed to rats in 3 therapeutic groups, respectively. The blood was collected to detect the concentration of Cr and BUN by ELISA. The kidney of each rat was collected to detect the concentration of renal injury factor (Kim-1) and the HE staining was performed. Western blot was used to detect the expression level of PI3K, p-AKT, AKT, PDK1, Skp2, and p27 in the renal tissue homogenate. Results: The symptom of vacuolar degeneration and interstitial edema was greatly improved in the rat kidney from the 3 therapeutic groups, compared with that from the RIRI model group. No significant difference was observed among the 3 therapeutic groups. The concentration of Cr in the 3 therapeutic groups was greatly lower than that in the RIRI model group. The expression level of p-AKT/AKT, PI3K, PDK1, Skp2, and p27 in OA group, LY294002 group, and OA combined with LY294002 group was significantly lower than that in the RIRI model group, respectively. Conclusion: OA could improve the symptom of RIRI, possibly by inhibiting PI3K/AKT signal pathway.

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Attenuation of renal ischemia/reperfusion injury by oleanolic acid preconditioning via its antioxidant, anti-inflammatory, and anti-apoptotic activities

Molecular Medicine Reports ◽

10.3892/mmr.2016.5128 ◽

2016 ◽

Vol 13 (6) ◽

pp. 4697-4704 ◽

Cited By ~ 20

Author(s):

CHENGMEI LONG ◽

JINRAN YANG ◽

HUA YANG ◽

XINCHANG LI ◽

GONGXIAN WANG

Keyword(s):

Reperfusion Injury ◽

Oleanolic Acid ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Renal Ischemia ◽

Renal Ischemia Reperfusion Injury ◽

Anti Inflammatory

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Renoprotective effect of curcumin labelled on Mesoscale Nanoparticles (MNPs) on Renal Ischemia-Reperfusion Injury (RIRI) via the miR-146a/nNOS/NO/cGMP/PKG signaling pathway

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666191009122035 ◽

2019 ◽

Vol 20 ◽

Cited By ~ 1

Author(s):

Wenjuan Ni ◽

Songlin Yu ◽

Fanshu Li ◽

Jiazhen Zhu ◽

Ziwei Chen ◽

...

Keyword(s):

Protective Effect ◽

Reperfusion Injury ◽

Signaling Pathway ◽

Caspase 3 ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Renal Ischemia ◽

Luciferase Assay ◽

Model Group ◽

Renal Ischemia Reperfusion Injury

: This study investigated the protective effect of Curcumin on renal ischemia-reperfusion injury (RIRI) as well as the mechanisms underlying the role of Curcumin. Selectivity of Curcumin in kidney in different doses and routes of administration was measured. In addition, the serum levels of β2-MG, UAER, BUN and creatinine were compared among the Sham, the RIRI model and the Curcumin + RIRI model groups. The expression of miR-146a iNOS, eNOS and nNOS, PKG, and caspase-3 among various groups was measured using real-time PCR and Western-blot analysis, while the levels of NO and cGMP in the samples were measured by ELISA. Finally, the effect of Curcumin on the transcriptional efficiencies of miR-146a, nNOS, eNOS and iNOS was studied using luciferase assay. The presence of mesoscale nanoparticles (MNPs) in the kidneys was safe. In addition, the accumulation of MNPs was in a dose-dependent manner and peaked at a dose of 25 mg/kg. The administration of Curcumin reduced the levels of serum β2-MG, UAER, BUN, creatinine as well as the score of renal tubule damage, therefore alleviating the symptoms induced by RIRI. Furthermore, the RIRI model group showed serious congestion and edema in the renal cortex and medulla, whereas the Curcumin + RIRI model group exhibited less renal tissue damage compared with that in the RIRI model group. Moreover, Curcumin enhanced miR-146a expression, while reducing the expression of nNOS, iNOS, cGPM, caspase-3 and PKG as well as the synthesis of NO. Curcumin may exert its effect by reducing the transcriptional efficiency of iNOS promoter, while increasing the transcriptional efficiency of miR-146a promoter. Furthermore, nNOS expression was negatively regulated by miR-146a. The protective effect of Curcumin against RIRI may be mediated by its regulation of cell apoptosis through the miR-146a/nNOS/NO/cGMP/PKG signaling pathway.

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Transplantation of chicken egg white extract-induced rabbit PBMCs as a treatment for renal ischemia-reperfusion injury in rabbits

PLoS ONE ◽

10.1371/journal.pone.0244160 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0244160

Author(s):

Guang-ping Ruan ◽

Xiang Yao ◽

Qing-keng Lin ◽

Zi-an Li ◽

Xue-min Cai ◽

...

Keyword(s):

Reperfusion Injury ◽

Mononuclear Cells ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Periodic Acid ◽

Renal Ischemia ◽

Model Group ◽

Periodic Acid Schiff ◽

Peripheral Blood Mononuclear ◽

Renal Ischemia Reperfusion Injury

Ischemia-reperfusion injury is an important contributor to acute kidney injury and a major factor affecting early functional recovery after kidney transplantation. We conducted this experiment to investigate the protective effect of induced multipotent stem cell transplantation on renal ischemia-reperfusion injury. Forty rabbits were divided into four groups of 10 rabbits each. Thirty rabbits were used to establish the renal ischemia-reperfusion injury model, and ten rabbits served as the model group and were not treated. Among the 30 rabbits with renal ischemia-reperfusion injury, 10 rabbits were treated with induced peripheral blood mononuclear cells (PBMCs), and 10 other rabbits were treated with noninduced PBMCs. After three weekly treatments, the serum creatinine levels, urea nitrogen levels and urine protein concentrations were quantified. The kidneys were stained with hematoxylin-eosin (HE), periodic acid-Schiff (PAS) and Masson’s trichrome and then sent for commercial metabolomic testing. The kidneys of the rabbits in the model group showed different degrees of pathological changes, and the recovery of renal function was observed in the group treated with induced cells. The results indicate that PBMCs differentiate into multipotent stem cells after induction and exert a therapeutic effect on renal ischemia-reperfusion injury.

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