Effects of gamma-butyrobetaine and mildronate on nitric oxide production in lipopolysaccharide-treated rats.
Production of nitric oxide was measured in lipopolysaccharide-treated rats (10 mg/kg, 4 hr) using the electron paramagnetic resonance method. As compared to the control animals, the nitric oxide level in liver of lipopolysaccharide-treated rats increased from 27.6+/-4.7 to 1485+/-129 ng/g tissue, in heart from 4.8+/-0.7 to 271+/-26 ng/g tissue, in blood from 33.6+/-12.4 to 638+/-136 ng/g tissue, in kidney from 3.3+/-0.5 to 356+/-31 ng/g tissue, in brain cortex from 46.0+/-3.4 to 227+/-27 ng/g tissue, in cerebellum from 27.7+/-2.6 to 218+/-30 ng/g tissue, and in testes from 13.8+/-1.1 to 86+/-8 ng/g tissue. Administration of the antiischaemic drug, mildronate (120 mg/kg) caused a significant twofold decrease of the nitric oxide level in brain cortex and cerebellum 1 hr after drug administration. Its natural analogue gamma-butyrobetaine (30 mg/kg) triggered a twofold decrease of the nitric oxide concentration in all studied tissues 30 min. after the administration. Nitric oxide reached the initial level 2 hr later. Neither mildronate nor gamma-butyrobetaine could inhibit the inducible nitric oxide synthase in vitro. Analogues of gamma-butyrobetaine appear to be prospective drugs for the treatment of circulatory complications of sepsis.
Sjakste
Nikolajs
N
Faculty of Medicine, University of Latvia, and Latvian Institute of Organic Synthesis, Riga. sjakste@osi.lv
Baumane
Larisa
L
Boucher
Jean-Luc
JL
Dzintare
Maija
M
Meirena
Dainuvite
D
Sjakste
Jelizaveta
J
Lauberte
Lasma
L
Kalvinsh
Ivars
I
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001622:Betaine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002331:Carnitine; D008070:Lipopolysaccharides; D008297:Male; D008763:Methylhydrazines / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D008070:Lipopolysaccharides; D008763:Methylhydrazines; D009569:Nitric Oxide; D001622:Betaine; C002889:gamma-butyrobetaine; C050147:3-(2,2,2-trimethylhydrazine)propionate; D002331:Carnitine