![]() ![]() This potentially lethal toxicity limits the use of this agent in cancer patients. Furthermore, repeated low-dose cisplatin administration may cause the acute kidney injury (AKI) to progress to chronic kidney disease with renal fibrosis ( 3). Approximately 1/3 of patients developed acute nephrotoxicity after a single dose of cisplatin ( 2). ![]() However, dose-dependent renal toxicity has been observed in clinical use and results in renal dysfunction and acute tubular necrosis ( 1). Thus, appropriate targeting of NOX2/ROS pathway may minimize the risk of cisplatin-induced kidney injury in patients receiving cancer therapy.Ĭisplatin is a common chemotherapy agent used to treat several kinds of cancers. Moreover, in cisplatin-induced AKI, intercellular adhesion molecule 1 (ICAM-1) and the chemoattractant CXC ligand 1 (CXCL1) were highly expressed in association with neutrophil infiltration, which were all attenuated by deletion of NOX2.Ĭonclusion: These data indicate that NOX2 aggravates cisplatin nephrotoxicity by promoting ROS-mediated tissue injury and neutrophil infiltration. ![]() NOX2 gene-knockout alleviated cisplatin-induced renal function decline, tubular injury score, kidney injury molecule-1(Kim-1) expression, and interleukin (IL)-6 and IL-1α levels with a reduction of ROS production. Results: We investigated the role of NOX2 in cisplatin-induced AKI and found that NOX2-mediated ROS production is a key inflammatory mediator of proximal tubular cell injury in cisplatin-induced AKI. Methods: A 8-10-week-old NOX2 gene-knockout and wild-type mice were injected with 25 mg/kg cisplatin intraperitoneally for experiments. However, its role in cisplatin-induced acute kidney injury (AKI) remains unknown. Reactive oxygen species (ROS) in the kidneys mainly arise from nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 2 (NOX2), which is highly upregulated during ischemia-reperfusion injury and diabetes mellitus. Cisplatin induces nephrotoxicity mainly through oxidative stress and inflammation. However, its high nephrotoxicity limits its therapeutic application and efficacy.
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