ABSTRACT

Purple corn extract (PCE) is a nutraceutical, an activator of AMPK, and it has antioxidants and anticancer properties. Therefore, PCE could be a candidate for alleviating cigarette smoke (CS)-induced oxidative DNA damage. This study examined whether PCE can have a protective effect on blood cells in an animal model of cigarette smoke (CS)-induced DNA damage. PCE was orally administered to CS-inhaled Spraque-Dawley (SD) rats, followed by the target cells being examined for markers of DNA damage. The study also sought to elucidate the mechanism of PCE action in the PCE treated animals. SD rat inhalation of CS was for once a day for 30 min, repeated for 7 days. PCE was administered orally before CS inhalation. Pretreatment of the animals with oral PCE kept the numbers of white blood cells (WBC) as well as neutrophils (NE), lymphocytes (LY), monocytes (Mo), eosinophils (EO), abd jasophils (BA) from increasing as those were increased in the CS-inhaling SD rats. The amount of phosphorylated γ-H2AX, a DNA damage marker, was assayed in the circulating blood cells collected from the animals and western blot analysis with anti-Foxo3a, p-Foxo3a, p-AMPK, MnSOD antibodies were performed on those cells. PCE protected the circulating blood cells from CS inhalation-induced DNA damage by 44% as assayed by increases in γ-H2AX. PCE also increased the nuclear localization of Foxo3a by 52% over control cells. Mechanistically, PCE appears to efficiently protect various blood cell types from CS-induced DNA damage through removal of ROS via activation of the AMPK/Foxo3a/MnSOD pathway.

摘要

紫玉米提取物（PCE）是一种营养保健品，是AMPK的活化剂，具有抗氧化剂和抗癌特性。因此，PCE可能是减轻香烟烟雾（CS）引起的氧化DNA损伤的候选药物。这项研究检查了PCE是否可以在香烟烟雾（CS）诱导的DNA损伤的动物模型中对血细胞产生保护作用。向吸入CS的Spraque-Dawley（SD）大鼠口服PCE，然后检查靶细胞的DNA损伤标志物。该研究还试图阐明PCE治疗动物中PCE作用的机制。SD大鼠每天一次吸入CS，持续30分钟，重复7天。吸入CS之前口服PCE。口服PCE对动物进行预处理可保留白细胞（WBC）以及中性粒细胞（NE），淋巴细胞（LY）的数量，随着吸入CS的SD大鼠中单核细胞（Mo），嗜酸性粒细胞（EO）和abd嗜碱性粒细胞（BA）的增加而增加。在从动物收集的循环血细胞中测定了磷酸化的γ-H2AX（一种DNA损伤标志物）的量，并用抗Foxo3a，p-Foxo3a，p-AMPK，MnSOD抗体对这些细胞进行了蛋白质印迹分析。PCE通过γ-H2AX的增加来保护循环血细胞免受CS吸入诱导的DNA损伤的44％。PCE还使Foxo3a的核定位比对照细胞增加了52％。从机理上讲，PCE似乎可以通过激活AMPK / Foxo3a / MnSOD途径去除ROS，有效地保护各种血细胞免受CS诱导的DNA损伤。在从动物收集的循环血细胞中测定了磷酸化的γ-H2AX（一种DNA损伤标志物）的量，并用抗Foxo3a，p-Foxo3a，p-AMPK，MnSOD抗体对这些细胞进行了蛋白质印迹分析。PCE通过γ-H2AX的增加来保护循环血细胞免受CS吸入诱导的DNA损伤的44％。PCE还使Foxo3a的核定位比对照细胞增加了52％。从机理上讲，PCE似乎可以通过激活AMPK / Foxo3a / MnSOD途径去除ROS，有效地保护各种血细胞免受CS诱导的DNA损伤。在从动物收集的循环血细胞中测定了磷酸化的γ-H2AX（一种DNA损伤标志物）的量，并用抗Foxo3a，p-Foxo3a，p-AMPK，MnSOD抗体对这些细胞进行了蛋白质印迹分析。PCE通过γ-H2AX的增加来保护循环血细胞免受CS吸入诱导的DNA损伤的44％。PCE还使Foxo3a的核定位比对照细胞增加了52％。从机理上讲，PCE似乎可以通过激活AMPK / Foxo3a / MnSOD途径去除ROS，有效地保护各种血细胞免受CS诱导的DNA损伤。PCE通过γ-H2AX的增加来保护循环血细胞免受CS吸入诱导的DNA损伤的44％。PCE还使Foxo3a的核定位比对照细胞增加了52％。从机理上讲，PCE似乎可以通过激活AMPK / Foxo3a / MnSOD途径去除ROS，有效地保护各种血细胞免受CS诱导的DNA损伤。PCE通过γ-H2AX的增加来保护循环血细胞免受CS吸入诱导的DNA损伤的44％。PCE还使Foxo3a的核定位比对照细胞增加了52％。从机理上讲，PCE似乎可以通过激活AMPK / Foxo3a / MnSOD途径去除ROS，有效地保护各种血细胞免受CS诱导的DNA损伤。