背景:曲霉毒素A(OTA),一种霉菌毒素,导致广泛的细胞损伤,影响肝脏和肾脏细胞。OTA毒性是相当好的特征,其中氧化应激被认为起作用,然而,OTA暴露后的分子事件序列,在文学中没有被描述。Further,减轻毒性的解毒剂报道很少。本研究的目的是了解OTA诱导毒性的一些分子机制的顺序以及槲皮素对OTA诱导毒性的细胞保护作用。
方法:进行了时程研究,以评估细胞内钙释放和ROS诱导的时间。两个关键的氧化还原敏感转录因子的激活和诱导时间,通过核定位和表达分别测定NF-κB和Nrf-2。测定炎性标志物COX-2的表达时间。研究了彗星试验对DNA的氧化损伤和微核形成。在所有上述参数下,还确定了槲皮素对OTA诱导的毒性的改善作用。
结果:OTA诱导的钙释放,ROS的产生和激活NF-κB的核转位和表达。槲皮素预处理可改善ROS和钙释放以及NF-κB的诱导和表达。槲皮素诱导Nrf-2核转位和表达。槲皮素的抗炎特性表现为下调COX-2。槲皮素在预防DNA损伤和微核形成方面具有明显的抗遗传毒性作用。
结论:槲皮素调节OTA诱导的HepG2细胞氧化应激和氧化还原信号传导。
结论:研究结果首次证明槲皮素可预防OTA诱导的HepG2细胞毒性。
BACKGROUND: Ochratoxin A (OTA), a mycotoxin, causes extensive cell damage, affecting liver and kidney cells. OTA toxicity is fairly well characterized where oxidative stress is believed to play a role, however, the sequence of molecular events after OTA-exposure, have not been characterized in literature. Further, antidotes for alleviating the toxicity are sparsely reported. The aim of this study was to understand the sequence of some molecular mechanisms for OTA-induced toxicity and the cytoprotective effect of quercetin on OTA-induced toxicity.
METHODS: Time course studies to evaluate the time of intracellular calcium release and ROS induction were carried out. The time of activation and induction of two key redox- sensitive transcription factors, NF-κB and Nrf-2 were determined by nuclear localization and expression respectively. The time of expression of inflammatory marker COX-2 was determined. Oxidative DNA damage by comet assay and micronucleus formation was studied. The ameliorative effect of quercetin on OTA-induced toxicity was also determined on all the above-mentioned parameters.
RESULTS: OTA-induced calcium release, ROS generation and activated NF-κB nuclear translocation and expression. Pre-treatment with quercetin ameliorated ROS and calcium release as well as NF-κB induction and expression. Quercetin induced Nrf-2 nuclear translocation and expression. Quercetin\'s anti-inflammatory property was exhibited as it down regulated COX-2. Anti-genotoxic effect of quercetin was evident in prevention of DNA damage and micronucleus formation.
CONCLUSIONS: Quercetin modulated OTA-induced oxidative stress and redox-signaling in HepG2 cells.
CONCLUSIONS: The results of the study demonstrate for the first time that quercetin prevents OTA-induced toxicity in HepG2 cells.