Study summary · research use only
Mechanistic Approach for Protective Effect of ARA290, a Specific Ligand for the Erythropoietin/CD131 Heteroreceptor, against Cisplatin-Induced Nephrotoxicity, the Involvement of Apoptosis and Inflammation Pathways
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this in vitro study using human HEK-293 and ACHN kidney cell lines, researchers pretreated cells with ARA290 (50-400 nM) before exposure to cisplatin (2.5 μM) to examine its effects on cisplatin-induced cell injury. ARA290 reduced DNA damage measured by comet assay and micronuclei frequency, lowered MDA/ROS levels while raising antioxidant enzyme levels, and reduced pro-inflammatory cytokines TNFα, IL6, and IL1β. Caspase-3 activity and tunnel assay indicated reduced apoptotic cell death, with gene and protein levels of TNFα, IL1β, IL6, Caspase-3, and Bax decreased and Bcl2 increased in the ARA290-plus-cisplatin group compared with cisplatin alone. The authors describe ARA290 as exerting anti-apoptotic, anti-inflammatory, and antioxidant effects against cisplatin-induced injury in these kidney cell models.
Abstract
ARA 290, an 11-amino acid linear nonhematopoietic peptide derived from the three-dimensional structure of helix B of the erythropoietin (EPO), interacts selectively with the innate repair receptor (IRR) that arbitrates tissue protection. The aim of this study was to investigate the protective effects of ARA290 against cisplatin-induced nephrotoxicity. For this purpose, HEK-293 and ACHN cells were treated with ARA290 (50-400 nM) and cisplatin (2.5 μM) in pretreatment condition. Then, cytotoxicity, genotoxicity, oxidative stress parameters (ROS, GPx, SOD, and MDA), and inflammatory markers (TNFα, IL6, and IL1β) were evaluated. Furthermore, apoptotic cell death was assessed via caspase-3 activity and tunnel assay. To determine the molecular mechanisms of the possible nephroprotective effects of ARA290, gene and protein expressions of TNFα, IL1β, IL6, Caspase-3, Bax, and Bcl2 were evaluated by real-time PCR and western blot assay, respectively. The findings indicated that ARA290 significantly reduced the DNA damage parameters of comet assay and the frequency of micronuclei induced by cisplatin. Besides, ARA290 improved cisplatin-induced oxidative stress by reducing MDA/ROS levels and enhancing antioxidant enzyme levels. In addition, reduced levels of pro-inflammatory cytokines indicated that cisplatin-induced renal inflammation was mitigated upon the treatment with ARA290. Besides, ARA290 ameliorates cisplatin-induced cell injury by antagonizing apoptosis. Furthermore, the molecular findings indicated that gene and protein levels of TNFα, IL1β, IL6, Caspase-3, and Bax were significantly decreased and gene and protein levels of Bcl2 significantly increased in the ARA290 plus cisplatin group compared with the cisplatin group. These findings revealed that ARA290 as a potent chemo-preventive agent exerted a protective effect on cisplatin-induced nephrotoxicity mostly through its anti-apoptotic, anti-inflammatory, and antioxidant potentials and also suggested that ARA290 might be a new therapeutic approach for patients with acute kidney injury.
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