Department of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan.
Toxicol In Vitro. 2013 Sep;27(6):1603-11. doi: 10.1016/j.tiv.2013.04.011. Epub 2013 Apr 30.
Melamine is a wildly used compound in manufactures of plastics and resins. A variety of toxic effects from melamine, including nephrolithiasis, chronic kidney inflammation, and bladder carcinoma, have been mentioned. Oxidative stress is considered to be an important pathogenic mechanism of kidney disease which may develop from an increasing free radical production through inflammation. The aim of this study is to investigate melamine-induced oxidative stress and inflammation in macrophage-like cell line RAW 264.7 and human embryonic kidney cell line HEK293. Results indicated melamine activated nuclear factor (NF)-κB through increasing IκB-α degradation and NF-κB p65/p50 DNA-binding activity. In addition, melamine significantly increased COX-2 expression and prostaglandin E2 (PGE2) production. Moreover, melamine activated NADPH oxidase (NOX), including NOX1, NOX2 and NOX4, accompanied with an increase in reactive oxygen species (ROS) production. Furthermore, melamine-induced ROS production could be attenuated by apocynin, a NOX inhibitor. In conclusion, our findings suggest melamine increased inflammation and oxidative stress via activation of NF-κB/COX-2 and NOX/ROS pathway, and first revealed the critical role of NOX in melamine-induced ROS production, suggesting the potential of NOX inhibitor against melamine toxicity.
三聚氰胺是一种广泛应用于塑料和树脂制造的化合物。三聚氰胺会引起多种毒性作用，包括肾结石、慢性肾炎症和膀胱癌等。氧化应激被认为是肾病的一个重要发病机制，它可能是通过炎症导致自由基产生增加而发展起来的。本研究旨在探讨三聚氰胺对巨噬细胞样细胞系 RAW 264.7 和人胚肾细胞系 HEK293 引起的氧化应激和炎症反应。结果表明，三聚氰胺通过增加 IκB-α 降解和 NF-κB p65/p50 DNA 结合活性来激活核因子（NF）-κB。此外，三聚氰胺显著增加了 COX-2 的表达和前列腺素 E2（PGE2）的产生。此外，三聚氰胺还激活了 NADPH 氧化酶（NOX），包括 NOX1、NOX2 和 NOX4，伴随着活性氧（ROS）的产生增加。此外，NOX 抑制剂 apocynin 可减轻三聚氰胺诱导的 ROS 产生。总之，我们的研究结果表明，三聚氰胺通过激活 NF-κB/COX-2 和 NOX/ROS 通路增加炎症和氧化应激，首次揭示了 NOX 在三聚氰胺诱导的 ROS 产生中的关键作用，提示 NOX 抑制剂可能对抗三聚氰胺毒性。
