E ffect of Nitric Oxide (NO) or Hydrogen Peroxide (H2O2) in the Nickel Induced cytotoxicity in RAW 264.7 Cell.
- Author:
Gyung Jae OH
1
;
Keun Sang KWON
Author Information
1. Department of Preventive Medicine and Public Health, School of Medicine Wonkwang University, Korea. pmokj@wonkwang.ac.kr
- Publication Type:Original Article
- Keywords:
Ni;
NO;
H2O2;
NMLA;
GSH;
ATP;
RAW 264.7 cell
- MeSH:
Abelson murine leukemia virus;
Adenosine Triphosphate;
Animals;
Arginine;
Catalase;
Cell Survival;
Dermatitis, Allergic Contact;
Dermatitis, Contact;
Hydrogen Peroxide*;
Hydrogen*;
Hypersensitivity;
Macrophages;
Mice;
Nickel*;
Nitric Oxide*;
Pathology;
Peroxynitrous Acid
- From:Korean Journal of Occupational and Environmental Medicine
2003;15(1):61-71
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
OBJECTIVES: Nickel (Ni) is present in many industrial working environments and consumer products, and is one of the leading cause of allergic contact dermatitis, which is a typical delayed (type IV) hypersensitivity reaction. However, the mechanism by which nickel causes this pathology is not well known. The contact dermatitis induced by nickel is mediated, primarily, through macrophages. This property was similar to autotoxicity related nitric oxide (NO) production. NO mediated cytotoxicity was dependent on both H2O2 and peroxynitrite (OONO-). The purpose of this study was to elucidate the role of NO/H2O2 in the cytotoxicity induced by nickel. Therefore, this study was designed to examine whether nickel could modulate NO/H2O2 production and how the Ni may affect ATP production, intracellular GSH level, and cell viability. METHODS: This study was based on the observations of cultures of RAW 264.7 cells, which originated from a tumor in a Balb/c mouse that had been induced by the Abelson murine leukemia virus. RAW 264.7 cells were treated with either Ni, N- onomethyl-L- arginine (NMLA), catalase, and DTT for 24-72 h. The cytotoxicity of the nickel was measured via the cell viability and NO2-, H2O2, GSH, and the mitochondrial function was evaluated by the adenosine triphosphate (ATP) production in the RAW 264.7 cells. RESULTS: The NO2- synthesis of RAW 264.7 cells increased with the increase in concentrations of Ni up to 50-micrometer, after 24 and 48 h of exposure, but then decreased at concentrations greater than 50-micrometer, and with time periods exceeding 48 h. In contrast, viability of cells and intracellular GSH level decreased in the presence of Ni in a dose and time dependent manner. However, the H2O2 synthesis of RAW 264.7 cells was not changed in the all experimental conditions. The NO2- synthesis of the cells was higher than control, whereas ATP, GSH and viability were lower than control in addition of Ni and the pretreatment of catalase or DTT prior to addition of Ni. CONCLUSIONS: These results suggest that NO plays an important role in the cytotoxicity of Ni. Cytotoxicity of Ni may exert through modulation of NO production and associate with a decrease in intracellular GSH levels.
