Protective Effects of Naringenin in a Rat Model of Sepsis-Triggered Acute Kidney Injury via Activation of Antioxidant Enzymes and Reduction in Urinary Angiotensinogen

Abstract

Background Sepsis is a devastating medical condition. In the USA, about 745 000 people are diagnosed with sepsis annually. Although many anti-inflammatory drugs have been used to manage sepsis, the treatment success rate is very low. This study was undertaken to examine the protective effects of naringenin on sepsis-induced kidney injury in rats. Material/Methods Sepsis was induced in Wistar albino rats by cecal ligation and puncture methods. Histological analysis was performed with hematoxylin and eosin (HE) staining. Reactive oxygen species (ROS) levels were determined by flow cytometery. TUNEL assay was used to demonstrate apoptosis. Sandwich ELISA method was used for the determination of urinary angiotensinogen, and protein expression was determined by Western blot analysis. Results We found that naringenin decreased atrophy in the glomerulus and enabled maintenance of the capsule area and normal tubular cavity of the septic rats. Admistration of naringenin at the dosage of 10 and 20 mg/kg to sepsis rats caused significant reduction in the sepsis-induced apoptosis of kidney cells, accompanied by decrease in Bax and increase in Bcl-2 expression. Moreover, naringenin also decreased the ROS levels in septic rats and downregulated the expression of SOD, CAT, and APX. The effects of naringenin were also examined on the levels of urinary angiotensinogen in sepsis rats. We found that naringenin caused a significant decrease in urinary angiotensinogen levels of septic rats. Conclusions Naringenin appears to have potential in the treatment of sepsis.

Smad3-Targeted Therapy Protects against Cisplatin-Induced AKI by Attenuating Programmed Cell Death and Inflammation via a NOX4-Dependent Mechanism

“…Lentivirus-mediated Smad3 KD prevented cisplatin-induced loss of renal function, inflammation, programmed cell death, and oxidative stress in mice. In addition, targeted inhibition of Smad3 by naringenin protects against cisplatin-induced AKI; this finding was consistent with the previous reports that naringenin showed renoprotective effects in response to other stimuli such as gentamicin [41][42][43].…”

TUNEL Assay: A Powerful Tool for Kidney Injury Evaluation

“…Cell death in neighboring cells starts unevenly because it depends on vascularization, cell cycle, and other variables. This often results in uneven TUNEL staining of cells in the tissue [ 45 , 96 , 125 ]. Surprisingly, the general intensity of the TUNEL-positive signal is not used for TUNEL measurement, despite it directly depending on the degree of DNA fragmentation.…”

“…Dispersed necrotic TUNEL was also observed during uranyl acetate-induced nephrotoxicity in mice [ 101 ]. Lastly, another TUNEL signal variable to pay attention to is the intensity of TUNEL-positive signals, which may deviate from cell to cell depending on the number of breaks (degree of injury) each cell experiences, as documented by some studies [ 45 , 96 , 125 ]. For models in which varying TUNEL signal intensity is observed, quantification by both the number of TUNEL-positive objects and the mean intensity of the staining is recommended.…”

Protective Effects of Naringenin from Citrus sinensis (var. Valencia) Peels against CCl4-Induced Hepatic and Renal Injuries in Rats Assessed by Metabolomics, Histological and Biochemical Analyses

“…Additionally, in parallel with the current findings, only a few reports have revealed the renoprotective effects of naringenin. It protected against sepsis-induced acute kidney injury in a previous study [ 69 ]. When combined with quercetin, naringenin ameliorated reno- and hepatotoxicity in rats [ 70 ].…”