Anti-inflammatory effects of 8-hydroxy-2 '-deoxyguanosine on lipopolysaccharide-induced inflammation via Rac suppression in Balb/c mice
- Authors
- Choi, Seongwon; Choi, Hyun-Ho; Lee, Sun-Hye; Ko, Seong-Hee; You, Ho-Jin; Ye, Sang-Kyu; Chung, Myung-Hee
- Issue Date
- 15-Dec-2007
- Publisher
- ELSEVIER SCIENCE INC
- Keywords
- 8-hydroxy-2 '-deoxyguanosine; acetyl salicylic acid; reactive oxygen species; Rac; inflammation; lipopolysaccharde; free radicals
- Citation
- FREE RADICAL BIOLOGY AND MEDICINE, v.43, no.12, pp 1594 - 1603
- Pages
- 10
- Journal Title
- FREE RADICAL BIOLOGY AND MEDICINE
- Volume
- 43
- Number
- 12
- Start Page
- 1594
- End Page
- 1603
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/14592
- DOI
- 10.1016/j.freeradbiomed.2007.08.022
- ISSN
- 0891-5849
1873-4596
- Abstract
- Recently, we observed that 8-hydroxyguanosine triphosphate and 8-hydroxy-2'-deoxyguanosine (oh(8)dG) inactivate Rac and consequently down-regulate the Rac-linked NADPH oxidase, iNOS, and Cox2. Based on these observations, we tested whether oh(8)dG has anti-inflammatory activity in vivo in lipopolysaccharide (LPS)-treated mice. LPS (1 mg/kg, ip)-treated mice exhibit marked inflammatory responses, including increases in proinflammatory cytokines (TNF-alpha, IL-6, IL-18, and IL-12p70) in serum and infiltration of neutrophils, increased translocation of NF-kappa B p50 from the cytosol to the nucleus, and phosphorylation of c-Jun in lung tissues. Mice were pretreated with oh(8)dG (up to 60 mg/kg, ip) 4 h before LPS injection, and this pretreatment dose-dependently inhibited the inflammatory responses; the inhibitions observed with 60 mg/kg oh(8)dG were statistically significant. At the same time, oh(8)dG pretreatment inactivated Rac in lung tissues. Oh(8)dG pretreatment (50 mg/kg, ip) also significantly protected against LPS-induced septic death. Furthermore, oh(8)dG was more effective than acetyl salicylic acid in inhibiting these inflammatory responses. 8-Hydroxyguanosine also had some effect but was much weaker than oh(8)dG. The effects of normal nucleosides (dG, G, and A) were negligible or not significant. These results support an anti-inflammatory activity for oh(8)dG, which could be ascribed to its Rac-inactivating action. (C) 2007 Elsevier Inc. All rights reserved.
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