Review Article J. Clin. Biochem. Nutr., 42, 8–13, January 2008 DjJ01TRKcCo980heybu18.Bevno3r20i2tnN1Je-o0a605w,pl040Jao8/A08ajnf0c96pre0bCatsi2necli.l?nSe?ioc.?ca?ile?BtpyioeocfchCemlinisictfrayl ynamic As t o RaNnudetrNituiotrntitiaionvndeThOeJxapyangesee ac nSocaientydof LNipiidt rpeircoxiOde xaniddFereeiRnadOicarlRaelsearch Cavity Eisuke F. Sato*, Tina Choudhury, Tomoko Nishikawa, and Masayasu Inoue 1Department of Biochemistry & Molecular Pathology, Osaka City University Medical School, Osaka, Osaka 545-8585, Japan ?? Received 3 September, 2007; Accepted 11 September, 2007 CopySriugmhtm©a2r0y08 OJCrBalNmucosa is a critical protective interface between external and internal envi- ronments. Therefore, it must serve as a barrier to a huge number of microbial species present in the environment. Saliva is an important factor that provides for the environment in the oral cavity, and it is indispensable to the host defense reaction in this manner. Oral neutrophils are also important contributors to maintaining the balance between health and disease in this complex environment. These produce reactive oxygen species, nitric oxide, and several antimi- crobial peptides, and enzymes. Neutrophils and saliva all contribute to the maintaining the health of the oral cavity in overlapping but independent ways. In addition to production by neutrophils and macrophage, some bacteria can also generate superoxide, hydrogen peroxide, and nitric oxide. Dietary intake of nitrate-enriched vegetables might play important roles in the protection of the oral and stomach against hazardous pathogens via the gastro-intestinal- salivary cycle of nitric oxide (NO) and related metabolites. This review will focus on defense system of the human oral cavity and metabolism of reactive oxygen and NO. Key Words: oral cavity, neutrophils, bacteria, superoxide, nitric oxide Introduction The oral cavity is a unique environment. Oral mucosa is a critical protective interface between external and internal en- vironments. Therefore, it must serve as a barrier to a huge number of microbial species present in the environment. Sa- liva is an important factor that provides for the environment in the oral cavity, and it is indispensable to the host defense reaction in this manner. Oral neutrophils are also important contributors to maintaining the balance between health and disease in this complex environment. These produce reac- *To whom correspondence should be addressed. Tel: +81-6-6645-3722 Fax: +81-6-6645-3721 E-mail: sato@med.osaka-cu.ac.jp He received “Lipid Peroxide and Free Radical Research Award” in 2006 in recognition of his outstanding work. 8 tive oxygen species, nitric oxide, and several antimicrobial peptides, the α-defensins, and other enzymes. Oral neutro- phils are part of the host innate immune response in this en- vironment. Neutrophils, and saliva all contribute to the maintaining the health of the oral cavity in overlapping but independent ways. This review will focus on defense system of the human oral cavity and include 1) the function of saliva and neutrophils in the oral cavity, 2) nitric oxide and reactive oxygen species of microbacteria which has led to advances in our understanding, and 3) functional efficacy against oral nitric oxide metabolism when it is known. Defense System of Oral Cavity Saliva is an important factor that provides for the environ- ment in the oral cavity, and it is indispensable to the host de- fense reaction in this manner. The continuous flow of saliva removes a large number of bacteria from teeth and mucosal