EPCK1, a vitamin C and E analogue, reduces endotoxin-induced systemic inflammation in mice.
BACKGROUND
Phosphate ester of vitamin C and vitamin E (EPCK1), a strong antioxidant, is a water- and lipid-soluble phosphate ester of vitamin C and vitamin E. In the current study, we tested whether EPCK1 inhibits oxidative stress and prevents systemic inflammation.


METHODS
Mice were randomly divided into a negative control group, a lipopolysaccharide (LPS)-induced sepsis group, and a group treated with an intraperitoneal infusion of EPCK1 (10 mg/kg) prior to or following LPS administration. In addition, RAW 264.7 cells were treated with LPS in the presence or absence of EPCK1. We examined levels of high mobility group box 1 (HMGB1) protein and inducible nitric oxide synthase (iNOS) in both in vivo and in vitro experiments, and liver histopathology in the in vivo experiment.


RESULTS
Liver histopathology significantly improved in the EPCK1 group compared with the LPS group. Although LPS administration increased HMGB1 and nitric oxide (NO) secretion, EPCK1 decreased the secretion of these mediators in vitro and in vivo.


CONCLUSIONS
Our findings suggest that EPCK1 may inhibit inflammation and potentially function as a novel anti-inflammatory therapeutic agent.
Shingu
Chihiro
C
Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Yufu City, Oita, Japan. cshingu@med.oita-u.ac.jp
Hagiwara
Satoshi
S
Iwasaka
Hideo
H
Matsumoto
Shigekiyo
S
Koga
Hironori
H
Yokoi
Isao
I
Noguchi
Takayuki
T
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002460:Cell Line; D004195:Disease Models, Animal; D004952:Esters / Q000494:pharmacology; D024243:HMGB1 Protein / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000276:immunology; D010710:Phosphates / Q000494:pharmacology; D018805:Sepsis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D015996:Survival Rate; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D004952:Esters; D024243:HMGB1 Protein; D008070:Lipopolysaccharides; D010710:Phosphates; D014810:Vitamin E; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D001205:Ascorbic Acid