Effects of intravenous infusion of highly purified vitamin B2 on lipopolysaccharide-induced shock and bacterial infection in mice.
We investigated the effect of an i.v. infusion of highly purified vitamin B(2) (riboflavin 5'-sodium phosphate: purity >97%) on lipopolysaccharide-induced shock and bacterial infection in mice. Six hours after lipopolysaccharide injection or 1 h after bacterial infection, vitamin B(2) or human activated protein C (APC) was administered by 6-h i.v. infusion. Vitamin B(2) at 10 mg/kg/6 h and up to 80 mg/kg/6 h significantly improved lipopolysaccharide-induced endotoxin shock. APC was also effective at low doses, but was deleterious at higher doses. Moreover, vitamin B(2) at 80 mg/kg/6 h significantly reduced the lethality of Escherichia coli and Staphylococcus aureus infection, whereas APC at up to 600 units/kg/6 h was ineffective. The i.v. infusion of vitamin B(2) reduced the elevations of proinflammatory cytokines and nitric oxide induced by lipopolysaccharide. These results suggest that i.v. infusion of vitamin B(2) represents a promising strategy for the treatment of sepsis and septic shock.
Toyosawa
Toshio
T
Tsukuba Research Laboratories, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan.
Suzuki
Mamoru
M
Kodama
Kohtarou
K
Araki
Seiichi
S
D000818:Animals; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000401:mortality; D007262:Infusions, Intravenous; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012256:Riboflavin / Q000008:administration & dosage / Q000627:therapeutic use*; D012772:Shock, Septic / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000401:mortality; D013211:Staphylococcus aureus; D013997:Time Factors
D008070:Lipopolysaccharides; D012256:Riboflavin