Tobacco smoking is a major risk factor for human cancers including urinary bladder carcinoma. In a previous study, nicotine enhanced rat urinary bladder carcinogenesis in a two-stage carcinogenesis model. Nicotine also induced cytotoxicity in the bladder urothelium in a short-term study. In the present study, male rats were treated with nicotine (40 ppm) in drinking water co-administered with the NADPH oxidase inhibitor, apocynin (0, 250 or 750 mg/kg) in diet for 4 weeks. The apocynin treatment induced no clinical toxic effects. Reduction of reactive oxygen species (ROS) by apocynin was confirmed by immunohistochemistry of 8-OHdG in the bladder urothelium. Incidences of simple hyperplasia, cell proliferation and apoptosis were reduced by apocynin treatment in the bladder urothelium. However, despite reduction of cell proliferation (labeling index), apocynin did not affect the incidence of simple hyperplasia, apoptosis, or ROS generation in the kidney pelvis urothelium, in addition to 8-OHdG positivity induced by nicotine being lower. In vitro, apocynin (500 µM) reduced ROS generation, but induced cell proliferation in bladder cancer cell lines (T24 and UMUC3 cells). These data suggest that oxidative stress may play a role in the cell proliferation of the bladder urothelium induced by nicotine.

中文翻译：

---

NADPH 氧化酶抑制剂罗布麻宁抑制尼古丁诱导的大鼠膀胱尿路上皮细胞增殖


吸烟是人类癌症（包括膀胱癌）的主要危险因素。在之前的一项研究中，尼古丁在两阶段致癌模型中增强了大鼠膀胱癌的发生。在一项短期研究中，尼古丁还诱导了膀胱尿道上皮的细胞毒性。在本研究中，雄性大鼠在饮用水中加入尼古丁（40 ppm），并在饮食中同时服用 NADPH 氧化酶抑制剂罗布麻宁（0、250 或 750 毫克/千克），为期 4 周。罗布麻宁治疗没有引起临床毒性作用。膀胱尿道上皮中 8-OHdG 的免疫组织化学证实了夹竹桃麻素可减少活性氧 (ROS)。夹竹桃麻素治疗膀胱尿道上皮，可减少单纯性增生、细胞增殖和细胞凋亡的发生率。然而，尽管罗布麻宁降低了细胞增殖（标记指数），但除尼古丁诱导的 8-OHdG 阳性率较低外，并没有影响肾盂尿路上皮单纯增生、凋亡或 ROS 生成的发生率。在体外，罗布麻素 (500 µM) 减少 ROS 生成，但诱导膀胱癌细胞系（T24 和 UMUC3 细胞）的细胞增殖。这些数据表明氧化应激可能在尼古丁诱导的膀胱尿道上皮细胞增殖中发挥作用。