<p>Activation of Nrf2 Signaling by Apelin Attenuates Renal Ischemia Reperfusion Injury in Diabetic Rats</p>

Abstract

Objective: Renal ischemia/reperfusion (I/R) injury is commonly seen in diabetic patients. Apelin has been demonstrated to protect against renal I/R injury, whereas detailed modulatory mechanisms by which Apelin exerts its role in renal I/R injury in diabetic patients remain unclarified. This research aimed to probe the functional molecules under the regulation of Apelin in renal I/R injury in diabetic rats. Materials and Methods: First, animal models were established for subsequent assays. Biochemical kits measured the serum levels of blood urea nitrogen (BUN) and serum creatinine (SCR), and hematoxylin and eosin (H&E) staining examined the histopathological changes of kidney tissues. Inflammatory factors containing tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), interleukin 6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) were tested through enzyme-linked immunosorbent assay (ELISA) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively. Reactive oxygen species (ROS) levels in the serum and kidney tissues were separately assessed by specific ROS kits. Cell apoptosis was further estimated through terminal deoxynucleotidyl transferasemediated dUTP nick end labeling (TUNEL) and Western blot analysis. Eventually, the influences of Apelin on nuclear factor erythroid 2-related factor (Nrf2) and its downstream genes were explored via Western blot analysis and immunohistochemistry (IHC). Results: In the present study, Apelin ameliorated the damage to renal function and histological structure, decreased levels of inflammatory factors and ROS, and hampered cell apoptosis in renal I/R injury of diabetic rats. Moreover, Apelin could elevate the levels of Nrf2 and downstream genes which were decreased under renal I/R injury. Conclusion: These data indicated that Apelin inhibited renal I/R injury through regulating Nrf2 signaling in diabetic rats, which might shed new light on the treatment of renal I/R injury in diabetic patients.

Ameliorative effect of apelin-13 against renal complications in L-NAME-induced preeclampsia in rats

“…It has also been reported that apelin inhibited renal dysfunction in adenine-induced chronic renal failure in rats ( Abul-fadle, Saied & Musa, 2018 ) and podocyte autophagy in diabetes ( Liu, Zhang & Wang, 2017 ). Furthermore, apelin ameliorated the affected renal function and histological structure, decreased inflammatory mediators and ROS, and hampered cell apoptosis in renal ischemia/reperfusion injury ( Bircan et al, 2016 and Zhang et al, 2020 ).…”

Loganin Attenuates Septic Acute Renal Injury with the Participation of AKT and Nrf2/HO-1 Signaling Pathways

“… 19 , 20 Previously, regulating Nrf2 and its downstream genes could decrease inflammatory factor release, reduce oxidative stress, and maintain anti-apoptotic and survival abilities in the injured kidney. 21 Therefore, restraining oxidative stress through activating Nrf2 pathway might be a possible therapeutic strategy targeting sepsis-related AKI.…”

Diuretic Action of Apelin-13 Mediated by Inhibiting cAMP/PKA/sPRR Pathway

“…Additionally, levels of apelin were altered in many disease models. For example, Zhang et al (2020) reported that Apln mRNA level increases both in the renal cortex and medulla in diabetic rats with renal ischemia-reperfusion injury, and apelin expression was significantly downregulated in pulmonary arterial hypertension and heart failure ( Yang et al, 2015 ). We previously reported that renal Apln mRNA expression was controlled by (pro)renin receptor (PRR) and significantly downregulated in high-salt-fed Dahl salt-sensitive rats ( Xu et al, 2020 ).…”