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Effects of cis ‐resveratrol on inflammatory murine macrophages: antioxidant activity and down‐regulation of inflammatory genes
Author(s) -
Leiro José,
Álvarez Ezequiel,
Arranz Juan A.,
Laguna Reyes,
Uriarte Eugenio,
Orallo Francisco
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1103561
Subject(s) - nicotinamide adenine dinucleotide phosphate , proinflammatory cytokine , reactive oxygen species , resveratrol , lipopolysaccharide , nitric oxide synthase , nitric oxide , superoxide , xanthine oxidase , nadph oxidase , chemistry , biochemistry , biology , inflammation , oxidase test , enzyme , immunology , endocrinology
This study investigated for the first time the effects of the cis isomer of resveratrol ( c ‐RESV) on the responses of inflammatory murine peritoneal macrophages, namely on the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) during the respiratory burst; on the biosynthesis of other mediators of inflammation such prostaglandins; and on the expression of inflammatory genes such as inducible nitric oxide synthase (NOS)‐2 and inducible cyclooxygenase (COX)‐2. Treatment with 1–100 μM c ‐RESV significantly inhibited intracellular and extracellular ROS production, and c ‐RESV at 10–100 μM significantly reduced RNS production. c ‐RESV at 1–100 μM was ineffective for scavenging superoxide radicals (O 2 •− ), generated enzymatically by a hypoxanthine (HX)/xanthine oxidase (XO) system and/or for inhibiting XO activity. However, c ‐RESV at 10–100 μM decreased nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase activity in macrophage homogenates. c ‐RESV at 100 μM decreased NOS‐2 and COX‐2 mRNA levels in lipopolysaccharide (LPS) interferon gamma (IFN‐γ)‐treated macrophages. At 10–100 μM, c ‐RESV also significantly inhibited NOS‐2 and COX‐2 protein synthesis and decreased prostaglandin E 2 (PGE 2 ) production. These results indicate that c ‐RESV at micromolar concentrations significantly attenuates several components of the macrophage response to proinflammatory stimuli (notably, production of O 2 •− and of the proinflammatory mediators NO • and PGE 2 ).