Cell proliferation of rat bladder urothelium induced by nicotine is suppressed by the NADPH oxidase inhibitor, apocynin. (1st January 2021)

• Record Type: Journal Article
• Authors: Suzuki, Shugo; Cohen, Samuel M.; Arnold, Lora L.; Pennington, Karen L.; Gi, Min; Kato, Hiroyuki; Naiki, Taku; Naiki-Ito, Aya; Wanibuchi, Hideki; Takahashi, Satoru
• Is Part Of: Toxicology letters. Volume 336(2021)
• Page Start: 32
• Page End: 38
• Publication Date: 2021-01-01
• Subjects: Nicotine -- Urinary bladder carcinogenesis -- Oxidative stress -- Apocynin -- Cell proliferation; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2020.11.005
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: Nicotine-induced simple hyperplasia in bladder urothelium was inhibited by apocynin. Nicotine-induced proliferation and apoptosis was suppressed by apocynin. ROS generation by nicotine was reduced by apocynin in the bladder urothelium. Oxidative stress may play a role in nicotine-induced proliferation of the urothelium. Abstract: 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.