Effect of Ionizing Radiation Exposure on NOX4 Expression in-Vitro and in-Vivo Studies: A Systematic Review and Meta-analysis

Abstract

Introduction: Patients exposed to ionizing radiation (IR) from various sources experience several side effects. Understanding the mechanisms through which IR induces these effects could minimize their consequences. This study investigates the activation pathway of NADPH oxidase 4 (NOX4) after exposure to IR. Methods: The analysis incorporated studies that assessed NOX4 expression as an outcome variable. The study involved searches across various databases. A total of 58 articles were included in the meta-analysis, and data extracted from these studies were analyzed using Comprehensive Meta-Analysis Software. Results: Analysis of the impact of IR on NOX4 expression, demonstrated a notable increase in protein expression in animals (SMD=3.452; p<0.001), in normal cells in vitro (SMD=2.689; p<0.001), and in cancer cells (SMD=2.159; p<0.05). Furthermore, there was a significant increase in NOX4 mRNA expression in animals (SMD=5.070; p<0.001), in normal cells in vitro (SMD=3.563; p<0.001), and in cancer cells (SMD=3.280; p<0.001). Subgroup analysis was conducted based on the tests utilized to measure NOX4 expression, various organs, IR parameters, and follow-up time after IR. Conclusion: NOX4 plays a crucial role in mediating radiation-induced damage in many organs. The upregulation of NOX4 expression in these organs is influenced by factors such as the radiation dose and source. Additionally, there was a further increase in NOX4 protein expression over time, highlighting its potential role in the progression of radiation-induced damage in vital organs.