ABSTRACT
Melatonin (in gum tragacanth as solvent) was administered to mice in the dose range of 100 to 450 mg/kg intraperitoneally. It prevented the increase in plasma glucose resulting from pancreatic toxicity caused by the intravenous administration of alloxan at 40 mg/kg. This action of melatonin was significant and dose-dependent. In parallel work using mouse brain homogenates, melatonin and more so its principal hepatic metabolite, 6-hydroxymelatonin, inhibited the formation of colored products reacting with thiobarbituric acid. Again, this inhibition was significant and dose-dependent. Alloxan-induced diabetes and lipoperoxidation induced by thiobarbituric acid are imputed to the production of oxygen free radicals. The consistent results obtained using these two experimental models show the antioxidant activity of melatonin, both in vivo and in vitro. This effect may be reasonably attributed to the indole structure of the molecule.
Subject(s)
Antioxidants/pharmacology , Diabetes Mellitus, Experimental/metabolism , Melatonin/pharmacology , Alloxan , Animals , Blood Glucose , Injections, Intraperitoneal , Lipid Peroxidation/drug effects , Male , Melatonin/analogs & derivatives , Mice , Thiobarbituric Acid Reactive Substances/metabolismABSTRACT
Gamma-hydroxybutyrate (GHB) administered to mice prior to alloxan antagonizes its diabetogenic action in a dose dependent fashion and up to 96 hours after injection. Results are discussed on the basis of free radical formation by alloxan and of the metabolic property of GHB which is known to increase the rate of operation of the pentose phosphate pathway.
Subject(s)
Diabetes Mellitus, Experimental/prevention & control , Sodium Oxybate/pharmacology , Alloxan/antagonists & inhibitors , Animals , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/metabolism , Free Radicals , Glucosephosphate Dehydrogenase/metabolism , Liver/drug effects , Liver/enzymology , Male , Mice , Pentose Phosphate Pathway/drug effectsABSTRACT
Rats were subjected to standard conditions of hemorrhagic shock. Animals were sacrificed 5 minutes and two hours after reinjection of blood which had effused into a syringe. The extent of shock was determined by measuring the acid base balance of the serum. Cerebral concentrations of NE, DA, DOPAC, HVA, 5-HT and 5-HIAA were measured and compared to controls. There was a significant decrease of the NE concentration and a highly significant increase of that of DA. Although the DOPAC concentration varied to a slight extent, that of HVA was significantly depressed 5 min after reinjection and exceeded initial values two hours later. It is consistent to interpret these results as a synaptic quiescence of DA utilization, which is no longer methylated by COMT. After two hours, however, extraneuronal DA metabolism was greatly increased, as indicated by the decreased DA concentration and the considerable increase of HVA levels. 5-HT turnover seemed to follow the same temporal variations, decreasing in the acute phase and then increasing during the recovery phase.
Subject(s)
Brain Chemistry , Catecholamines/metabolism , Serotonin/metabolism , Shock, Hemorrhagic/metabolism , Animals , Blood Gas Analysis , Blood Pressure , Dopamine/metabolism , Male , Norepinephrine/metabolism , Rats , Rats, Inbred StrainsABSTRACT
Different associations of pharmacological agents were tested in the curative treatment of hemorrhagic shock, using as criteria the variations of cerebral biogenic amines (NE, DA, 5-HT) and some of their metabolites (DOPAC, HVA, 5-HIAA). These values were compared to those observed in controls two hours after the reinjection of effused blood. Prior work had led to the use of each component of these therapeutic associations and the reasons having suggested their association are summarized. The results show that the most active association for antagonizing the changes of the above amines and metabolites is that of tyrosine, 15% glucose, insulin and vitamin C. The results are discussed.
