The present study was aimed at assessing the impact of AgNPs on the liver of male rats orally exposed to 0, 50, 100 and 200 mg/kg/day of polyvinyl pyrrolidone coated AgNPs (PVP-AgNPs) for 90 days. The induction of apoptotic cell death -by measuring the protein levels of the active form of caspase 3- and the levels of the microtubule-associated protein 1A/1B-light chain (LC3) protein were measured as a marker of the induction of autophagy. PVP-AgNPs caused an increase of the activity of superoxide dismutase (SOD) and catalase (CAT) in the liver of male rats. However, the activity decreased after exposure to high amounts of PVP-AgNPs. Increased protein levels of IRS-1, AKT, GSK3β and mTOR proteins were observed in a dose-dependent manner. However, these proteins showed a decrease at 200 mg/kg/day. The same pattern was observed for the p53, p21 and cleaved caspase 3 protein levels. The current results suggest that the increase of ROS production by PVP-AgNPs stimulated SOD and CAT activity, as well as IRS-1, AKT, mTOR, p53, p21 and caspase 3 as protective mechanisms of cell survival and preserve DNA fidelity. However, cellular damage by excessive ROS production might induce the depletion of these survival mechanisms at 200 mg/kg/day.

本研究旨在评估AgNPs对口服暴露于0、50、100和200 mg / kg / day的聚乙烯吡咯烷酮包被的AgNPs（PVP-AgNPs）90天的雄性大鼠肝脏的影响。通过测量胱天蛋白酶3的活性形式的蛋白水平和微管相关蛋白1A / 1B-轻链（LC3）蛋白的水平来诱导凋亡细胞死亡，作为自噬诱导的标志物。PVP-AgNPs导致雄性大鼠肝脏中超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的活性增加。但是，暴露于大量的PVP-AgNPs后，活性降低。观察到IRS-1，AKT，GSK3β和mTOR蛋白的蛋白质水平呈剂量依赖性。但是，这些蛋白质在200 mg / kg / day时下降。对于p53，观察到相同的模式，p21和裂解的caspase 3蛋白水平。目前的结果表明，PVP-AgNPs ROS产生的增加刺激了SOD和CAT活性，以及​​IRS-1，AKT，mTOR，p53，p21和caspase 3作为细胞存活的保护机制并保持了DNA保真度。但是，过量ROS产生的细胞损伤可能会导致这些生存机制耗竭200 mg / kg / day。