Saccharated colloidal iron enhances lipopolysaccharide-induced nitric oxide production in vivo.
We investigated the effects of iron on the production of nitric oxide (NO), inducible NO synthase (iNOS), and plasma cytokines induced by lipopolysaccharide (LPS) in vivo. Male Wistar rats were preloaded with a single intravenous injection of saccharated colloidal iron (Fesin, 70 mg iron/kg body weight) or normal saline as a control, and then given an intraperitoneal injection of LPS (5.0 mg/kg body weight). Rats, preloaded with iron, had evidence of both iron deposition and strong iNOS induction in liver Kupffer cells upon injection of LPS; phagocytic cells in the spleen and lung had similar findings. LPS-induced NO production in iron-preloaded rats was significantly higher than control rats as accessed by NO-hemoglobin levels measured by ESR (electron spin resonance) and NOx (nitrate plus nitrite) levels. Western blot analysis showed that iron preloading significantly enhanced LPS-induced iNOS induction in the liver, but not in the spleen or lung. LPS-induced plasma levels of IL-6, IL-1beta, and TNF-alpha were also significantly higher in iron-preloaded rats as shown by ELISA, but IFN-gamma levels were unchanged. We conclude that colloidal-iron phagocytosed by liver Kupffer cells enhanced LPS-induced NO production in vivo, iNOS induction in the liver, and release of IL-6, IL-1beta, and TNF-alpha.
Hida
Akira I
AI
Pathological Research, Department of Biopathological Science, Graduate School of Medicine and Dentistry, Okayama University, 2-5-1 Shikata, Okayama 700-8558, Japan. aihida@mac.com
Kawabata
Teruyuki
T
Minamiyama
Yukiko
Y
Mizote
Akiko
A
Okada
Shigeru
S
D000818:Animals; D003102:Colloids / Q000494:pharmacology*; D004357:Drug Synergism; D004578:Electron Spin Resonance Spectroscopy; D006454:Hemoglobins / Q000378:metabolism; D006878:Hydroxides / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D009930:Organic Chemicals; D010587:Phagocytosis; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects / Q000201:enzymology
D003102:Colloids; D006454:Hemoglobins; D006878:Hydroxides; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D009930:Organic Chemicals; C083971:colloidal iron hydroxide; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat