Trans-resveratrol alone and hydroxystilbenes of rhubarb (Rheum rhaponticum L.) root reduce liver damage induced by chronic ethanol administration: a comparative study in mice.

The hepatoprotective effects and pharmacokinetics of trans-resveratrol and hydroxystilbenes of the garden rhubarb (Rheum rhaponticum L., R. rhaponticum) root ethanol extract were studied. Ethanol was administered to male BALB/c mice for 35 days in an inhalation chamber. During this time vehicle, trans-resveratrol (20 mg/kg per day) or R. rhaponticum extract was intraperitoneally (i.p.) administered and mice were sacrificed for the collection of liver and blood. In an additional experiment, the level of parent compounds and metabolites was estimated in the blood after acute i.p. administration of trans-resveratrol or R. rhaponticum extract. The levels of hydroxystilbenes, their metabolites and fatty acid oxy-metabolites (oxylipins) were studied by LC-tandem DAD-MS/MS. Ethanol induced hepatotoxicity, as evidenced by histological changes and accumulation of oxylipins in the blood. Both trans-resveratrol and R. rhaponticum extract reduced the extent of these changes. The pharmacokinetics of trans-resveratrol was characterized by a rapid removal from the blood and metabolism to sulfates and glucuronides. After the administration of R. rhaponticum extract, in addition to trans-resveratrol glucoside and its metabolites, several other hydroxystilbenes were found. Inhibition of oxidation of polyunsaturated fatty acids is proposed as a basis of the hepatoprotective effect of both trans-resveratrol and R. rhaponticum extract.

Litter has an effect on the behavioural changes caused by the administration of the nitric oxide synthase inhibitor NG-nitro-L-arginine and ethanol in mice.

The aim of the work was to study the effects of litter and the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine (L-NOARG) on the behaviour of mice after acute and chronic ethanol administration and withdrawal. Male outbred NIH/S mice, from 21 litters, were distributed among experimental groups and subjected to acute and chronic ethanol administration. After acute or chronic ethanol administration, the effects of L-NOARG on the behaviour of mice in the plus-maze test were studied. Acute ethanol (1 g/kg, i.p.), L-NOARG (20 and 40 mg/kg, i.p.) and their combination induced an anxiolytic effect. Furthermore, the values for the representatives of different litters tended to be either above or below the group mean, irrespective of the drug treatment. Chronic ethanol administration (23 days by inhalation) induced an anxiolytic effect and ethanol withdrawal induced an anxiogenic effect in the plus-maze. The administration of L-NOARG (20 mg/kg, i.p.) induced an anxiolytic effect in control mice and had no effect on ethanol-intoxicated mice, but attenuated the anxiogenic effect of ethanol withdrawal in the plus-maze. However, after chronic ethanol administration and withdrawal, litter had no effect on the behaviour of mice. If the litter is a significant determinant in the behaviour of outbred mice, then the use of information about the litter origin of animals could serve for the purposes of reduction. But only if this information is available from breeders.

Effects of nitric oxide synthase inhibitors 7-NI, L-NAME, and L-NOARG in staircase test.

BACKGROUND: The objective of the study was to investigate the effects of the nitric oxide synthase (NOS) inhibitors 7-nitroindazole (7-NI), N(G)-nitro-L-arginine (L-NOARG), and N(G)-nitro-L-arginine methyl ester (L-NAME) on the behavior of mice in the staircase test. METHODS: NOS inhibitors 7-NI (20-120 mg/kg), L-NOARG (20 and 40 mg/kg), and L-NAME (20 and 40 mg/kg) were administered intraperitoneally (i.p.) 30 min prior to the staircase test. Staircase test consisted of placing a mouse in an enclosed staircase with five steps and recording the number of rearings made and the number of steps climbed during a 3-min period. RESULTS: 7-NI and L-NOARG did not have a significant effect on the behavior of mice in the staircase test. L-NAME caused a decrease in the number of rearings without changes in the number of steps taken. CONCLUSIONS: NOS inhibitor L-NAME but not 7-NI or L-NAME induced an anxiolytic effect in the staircase test.

The effects of the nitric oxide synthase inhibitors on the behaviour of small-platform-stressed mice in the plus-maze test.

Effects of the nitric oxide synthase (NOS) inhibitors 7-nitroindazole (7-NI), N(G)-nitro-L-arginine (L-NOARG) and N(G)-nitro-L-arginine methyl ester (L-NAME) on the behaviour of control and small-platform (SP)-stressed mice in the plus-maze test were studied. SP stress was induced by placing mice on SPs (3.5 cm diameter) surrounded by water for 24 h. This model contains several factors of stress like rapid eye movement (REM) sleep deprivation, isolation, immobilization and falling into the water. The plus-maze test was carried out with control and SP-stressed mice. SP stress induced an anxiolytic-like effect that was evidenced by increased percentage of time spent on the open arms of the plus-maze. The administration of NOS inhibitors 7-NI (20.0-120.0 mg/kg) and L-NOARG (20.0 and 40.0 mg/kg) induced an anxiolytic effect and the administration of L-NAME (20.0 and 40.0 mg/kg)--an anxiogenic effect in control mice. In SP-stressed mice, the effects of NOS inhibitors were changed. Contrary to control mice, 7-NI at a dose of 20.0 mg/kg induced an anxiogenic effect in SP-stressed mice and other doses of 7-NI, with exception of 80.0 mg/kg, as well as L-NOARG and L-NAME were without any effect. On the basis of these data, we can propose that SP stress induced changes in the function of L-arginine-NOS-NO pathways. It is also proposed that the behavioural effects of NOS inhibitors can be changed in stressed animals.