Nephroprotective Effect of Embryonic Stem Cells Reducing Lipid Peroxidation in Kidney Injury Induced by Cisplatin

Abstract

Introduction. The acute kidney injury (AKI) is characterized by a sudden glomerular filtration reduction. Renal or intrinsic causes of AKI include nephrotoxicity induced by exogenous agents like cisplatin, which causes oxidative stress altering the biochemical process and leading to apoptosis. Therefore, this research is aimed at analyzing the embryonic stem cells (ESC) nephroprotective effect in AKI induced by cisplatin, employing genetic, phenotypic, and microspectroscopic techniques. Methods. Thirty mice were randomly divided into three groups (n=10): the healthy, isotonic salt solution (ISS), and mouse embryonic stem cells (mESC) groups. The ISS and mESC groups were subjected to AKI using cisplatin; 24 h post-AKI received an intraperitoneal injection of ISS or 1×106 mESC, respectively. At days 4 and 8 post-AKI, five mice of each group were sacrificed to analyze the histopathological, genetic (PDK4 and HO-1), protein (p53), and vibrational microspectroscopic changes. Results. Histopathologically, interstitial nephritis and acute tubular necrosis were observed; however, the mESC group showed a more preserved microarchitecture with high cellularity. Additionally, the PDK4 and HO-1 gene expression only increased in the ISS group on day 4 post-AKI. Likewise, p53 was more immunoexpressed at day 8 post-AKI in the ISS group. About biomolecular analysis by microspectroscopy, bands associated with lipids, proteins, and nucleic acids were evidenced. Besides, ratios related to membrane function (protein/lipid), unsaturated lipid content (olefinic/total lipid, olefinic/total CH2, and CH2/CH3), and lipid peroxidation demonstrated oxidative stress induction and lipid peroxidation increase mainly in the ISS group. Finally, the principal component analysis discriminated against each group; nonetheless, some data of the healthy and mESC groups at day 8 were correlated. Conclusions. The mESC implant diminishes cisplatin nephrotoxicity, once the protective effect in the reduction of lipid peroxidation was demonstrated, reflecting a functional and histological restoration.

Remote Ischemic Preconditioning Protects Cisplatin-Induced Acute Kidney Injury through the PTEN/AKT Signaling Pathway

“…To investigate the protective effects of RIPC on Cis-induced AKI mice, we constructed a RIPC pretreatment animal model following the procedure in Figure 1(a). It was frequently observed that the Cis-induced AKI mice exhibit the elevation of serum creatinine (CRE) and blood urea nitrogen (BUN) level, which are closely linked to renal function [28, 29]. Indeed, we observed that the serum CRE and BUN concentrations were significantly increased to 2.9- and 4.3-fold of Con group after Cis treatment (20 mg/kg) (Figures 1(b) and 1(c)), respectively, suggesting the kidney and animals receive a serious damage.…”

“…It was well documented that tubular epithelial cell apoptosis plays crucial roles in the pathogenesis of Cis-induced AKI [30, 31]. To further demonstrate that RIPC protects the kidney from Cis-induced AKI in a miR-144-mediated manner, we manipulated the expression of miR-144 using a well-worked antago-miR [28, 29]. Firstly, we checked the expression of miR-144 using real-time qPCR and found its expression was dramatically downregulated (Figure 4(a)).…”

Stem cells: a potential treatment option for kidney diseases

“…Glomerulosclerosis or collapsed glomeruli were not observed in RFI mice treated with mESCs; even some regeneration data were found characterized by large nuclei with prominent [37]. Mata-Miranda et al suggested the beneficial effects of mESCs on AKI were related to the reduction of lipid peroxidation [38].…”

The Cross‐Link between Ferroptosis and Kidney Diseases

“…Oxidative injury mediated by lipid peroxidation is an unfavorable factor for AKI [ 85 ], while lipid peroxidation inhibition can alleviate kidney injury [ 86 ]. One month before Dixon proposed ferroptosis, some researchers found that deferoxamine (DFO), which was not listed as a ferroptosis inhibitor then, could inhibit lipid peroxidation and renal tubular epithelial cell necrosis to prevent renal failure [ 87 ].…”