Effects of co-administration of dietary sodium arsenite and an NADPH oxidase inhibitor on the rat bladder epithelium

Shugo Suzuki, Lora L. Arnold, Karen L. Pennington, Satoko Kakiuchi-Kiyota, Samuel M. Cohen

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Arsenite (AsIII), an inorganic arsenical, is a known human carcinogen, inducing tumors of the skin, urinary bladder and lung. It is metabolized to organic methylated arsenicals. Oxidative stress has been suggested as a mechanism for arsenic-induced carcinogenesis. Reactive oxygen species (ROS) can be important factors for carcinogenesis and tumor progression. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is known to produce intracellular ROS, therefore, we investigated the ability of apocynin (acetovanillone), an NADPH oxidase inhibitor, to inhibit the cytotoxicity and regenerative cell proliferation of arsenic in vitro and in vivo. Apocynin had similar effects in reducing the cytotoxicity of AsIII and dimethylarsinous acid (DMAIII) in rat urothelial cells in vitro. When tested at the same concentrations as apocynin, other antioxidants, such as l-ascorbate and N-acetylcysteine, did not inhibit AsIII-induced cytotoxicity but they were more effective at inhibiting DMAIII-induced cytotoxicity compared with apocynin. In vivo, female rats were treated for 3 weeks with 100 ppm AsIII. Immunohistochemical staining for 8-hydroxy-2′-deoxyguanosine (8-OHdG) showed that apocynin reduced oxidative stress partially induced by AsIII treatment on rat urothelium, and significantly reduced the cytotoxicity of superficial cells detected by scanning electron microscopy (SEM). However, based on the incidence of simple hyperplasia and the bromodeoxyuridine (BrdU) labeling index, apocynin did not inhibit AsIII-induced urothelial cell proliferation. These data suggest that the NADPH oxidase inhibitor, apocynin, may have the ability to partially inhibit arsenic-induced oxidative stress and cytotoxicity of the rat bladder epithelium in vitro and in vivo. However, apocynin did not inhibit the regenerative cell proliferation induced by arsenite in a short-term study.

Original languageEnglish (US)
Pages (from-to)41-46
Number of pages6
Issue number1-2
StatePublished - Jun 30 2009


  • Arsenite (As)
  • Dimethylarsinous acid (DMA)
  • Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
  • Urinary bladder
  • Urothelial cell cytotoxicity

ASJC Scopus subject areas

  • Toxicology


Dive into the research topics of 'Effects of co-administration of dietary sodium arsenite and an NADPH oxidase inhibitor on the rat bladder epithelium'. Together they form a unique fingerprint.

Cite this