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Renoprotective Effect of Curcumin Labelled on Mesoscale Nanoparticles (MNPs) in Renal Ischemia-Reperfusion Injury (RIRI) via the miR-146a/ nNOS/NO/cGMP/PKG Signaling Pathway

[ Vol. 21 , Issue. 3 ]

Author(s):

Wenjuan Ni, Songlin Yu, Fanshu Li, Jiazhen Zhu, Ziwei Chen, Shujuan Li, Shanshan Hou and Fuhe Liu*   Pages 244 - 255 ( 12 )

Abstract:


Background & Objective: This study investigated the possible renoprotective effect of curcumin against Renal Ischemia-Reperfusion Injury (RIRI) and its possible underlying mechanisms. A total of 36 SD rats were recruited and allocated into a sham group, a RIRI model group, and a CUR + RIRI group with 12 rats in each group. Among them, rats in the CUR+RIRI group were specially treated with 100 mg/kg curcumin. The selectivity of curcumin in the kidney in different doses and routes of administration was measured. In addition, the serum levels of beta-2 microglobulin (β2-MG), Urinary Albumin Excretion Rate (UAER), Blood Urea Nitrogen (BUN) and creatinine were compared among the sham, the RIRI model and the curcumin + RIRI model groups.

Methods: The expression of miR-146a, inducible NOS (iNOS), endothelial NOS (eNOS) and neuronal NOS (nNOS), protein kinase G (PKG), and caspase-3 among various groups was measured using realtime PCR and Western-blot analysis, while the levels of NO and cyclic guanosine monophosphate (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.

Results: The presence of mesoscale nanoparticles (MNPs) in the kidneys was safe. Also, 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, and 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 the 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 the iNOS promoter, while increasing the transcriptional efficiency of miR-146a promoter.

Conclusion: 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.

Keywords:

Nanoparticle, curcumin, RIRI, miR-146a, nNOS, NO, cGMP, PKG, apoptosis.

Affiliation:

Zhejiang Pharmaceutical College, Ningbo, Zhejiang, 315100, PR, Zhejiang Pharmaceutical College, Ningbo, Zhejiang, 315100, PR, College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 311402, PR, College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 311402, PR, Zhejiang Pharmaceutical College, Ningbo, Zhejiang, 315100, PR, Zhejiang Pharmaceutical College, Ningbo, Zhejiang, 315100, PR, Zhejiang Pharmaceutical College, Ningbo, Zhejiang, 315100, PR, Zhejiang Pharmaceutical College, Ningbo, Zhejiang, 315100, PR



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