Protective effect of vitamin D3 analogues on endotoxin shock in mice.
The effect of vitamin D3 analogues on endotoxin shock in mice was investigated. Male ICR mice were orally administered vitamin D3 analogues or vehicle, accompanied by an intraperitoneal injection of endotoxin (E. Coli lipopolysaccharide, LPS, 20 mg/kg). Endotoxin caused a decrease in survival rate in a time-dependent manner. Increases in plasma immunoreactive (i) eicosanoid and hepatic malondialdehyde (MDA) levels were also observed. Administration of 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) improved the survival rate 24 to 48 h after endotoxin treatment. The effects were markedly observed at a dose of 20 ng/kg. In addition, 1 alpha-OH-D3 restored the plasma iTXB2 and hepatic MDA levels 8 h after endotoxin injection. However, it did not affect plasma iPGE2, i6-keto-PGF1 alpha and blood iLTB4 levels. At a dose of 20 ng/kg, both 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and 1,24(R)-dihydroxyvitamin D3 (1,24(R)-(OH)2D3) restored the survival rate, the plasma iTXB2 and hepatic MDA levels. These results suggest that vitamin D3 analogues may inhibit endotoxemia through regulation of the formation of TXA2 and free radicals.
Horiuchi
H
H
Pharmacological Research Department, Teijin Institute for Bio-Medical Research II, Tokyo, Japan.
Nagata
I
I
Komoriya
K
K
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology; D002762:Cholecalciferol / Q000494:pharmacology*; D004100:Dihydroxycholecalciferols / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004731:Endotoxins; D007975:Leukotriene B4 / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde; D051379:Mice; D008813:Mice, Inbred ICR; D011863:Radioimmunoassay; D012772:Shock, Septic / Q000517:prevention & control*; D013929:Thromboxane B2 / Q000378:metabolism
D004100:Dihydroxycholecalciferols; D004731:Endotoxins; D002762:Cholecalciferol; D007975:Leukotriene B4; D008315:Malondialdehyde; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C023850:1 alpha,24-dihydroxyvitamin D3; C044101:endotoxin, Escherichia coli; D002117:Calcitriol; D015232:Dinoprostone