[Molecular mechanisms of antioxidant action of dalargin on the liver in experimental cholestasis].
Changes of antioxidant activity of dalargin in the liver after naloxone (100 micrograms/kg) administration were examined in experiment on 144 rats with cholestasis. It was found that dalargin inhibited the activity of xanthine oxidase by 32-37% in different time periods after the injection. Dalargin and naloxone, when used in combination, had no effect on the enzyme activity. Glutathione-S-transferase activity rose by 38.0% and 21.8% on hour 1 and 3 after the injection, respectively, while simultaneous injection of dalargin and naloxone induced no changes in the enzyme activity after 1 hour, though decreased it by 36.8% and 26.4% on hour 3 and 5, respectively. Dalargin inhibited lipid peroxidation by 29-35%, simultaneous injection of dalargin and naloxone raised lipid peroxidation by 109.2%, 80.7% and 25.7% after 1, 3 and 5 hours, respectively. Dalargin injection elucidated a marked tendency to lowering of blood release of the liver-specific enzymes histidase and urokaninase in line with enhancement of their activity in the liver. A combined injection of dalargin and naloxone promoted high release of histidase and urokaninase in blood and did not change histidase activity in the liver in all cases. Urokanidase activity elevated in 5 hours. It was noticed that dalargin raised leu-enkephalin levels in the liver 3.5-fold 1 h after the injection. The reduced dalargin antioxidant effect coupled with naloxone pretreatment demonstrated indirect action of the neuropeptide on the liver via neuron receptors of the liver.
Korotkina
R N
RN
Fomchenkov
E P
EP
Andreev
V I
VI
Smirnova
V I
VI
Karelin
A A
AA
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002779:Cholestasis / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D016308:Enkephalin, Leucine-2-Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D013565:Sympatholytics / Q000494:pharmacology*; D013997:Time Factors
D000975:Antioxidants; D013565:Sympatholytics; D009270:Naloxone; D016308:Enkephalin, Leucine-2-Alanine; C040996:enkephalin-Leu, Ala(2)-Arg(6)-