Premium
Effects of γ‐Butyrobetaine and Mildronate on Nitric Oxide Production in Lipopolysaccharide‐Treated Rats
Author(s) -
Sjakste Nikolajs,
Baumane Larisa,
Boucher JeanLuc,
Dzintare Maija,
Meirena Dainuvite,
Sjakste Jelizaveta,
Lauberte Lasma,
Kalvinsh Ivars
Publication year - 2004
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2004.pto_940108.x
Subject(s) - nitric oxide , lipopolysaccharide , chemistry , nitric oxide synthase , pharmacology , cerebellum , medicine , endocrinology
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 γ‐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 γ‐butyrobetaine could inhibit the inducible nitric oxide synthase in vitro . Analogues of γ‐butyrobetaine appear to be prospective drugs for the treatment of circulatory complications of sepsis.