ABSTRACT
The bioassay guided fractionation of the dried aerial part of Indigofera tinctoria Linn. led to the identification of an active fraction labelled as indigotin. On further chemical analysis, a compound isolated from indigotin was identified and characterized as trans-tetracos-15-enoic acid (TCA). The chemical structure of this compound was established on the basis of physical properties and spectral data, including NMR. It afforded significant hepatoprotection against carbon tetrachloride and paracetamol induced hepatotoxicity in experimental models. Silymarin, a well known plant based hepatoprotective agent, and N-acetylcysteine, which has proven efficacy as a replenisher of sulfhydryls, were used for relative efficacy. TCA was found to reverse the altered hepatic parameters in experimental liver damage. In the safety evaluation study the oral LD50 was found to be more than 2000 mg/kg, with no signs of abnormalities or any mortality for the 15 day period of observation after administration of a single dose of drug in mice. The studies revealed significant and concentration dependent hepatoprotective potential of TCA as it reversed the majority of the altered hepatic parameters in experimental liver damage in rats and mice and may be useful in the management of liver disorders.
Subject(s)
Fatty Acids, Monounsaturated/therapeutic use , Indigofera/chemistry , Liver Diseases/drug therapy , Phytotherapy , Acetaminophen , Animals , Carbon Tetrachloride , Chemical and Drug Induced Liver Injury , Fatty Acids, Monounsaturated/chemistry , Fatty Acids, Monounsaturated/isolation & purification , Female , Hexobarbital/pharmacology , Hypnotics and Sedatives/toxicity , Inert Gas Narcosis/drug therapy , Male , Mice , Nuclear Magnetic Resonance, Biomolecular , Paralysis/chemically induced , Protective Agents/chemistry , Protective Agents/isolation & purification , Protective Agents/therapeutic use , Rats , Rats, Wistar , ZoxazolamineABSTRACT
Involvement of the adrenergic mediator system in central mechanisms of hyperbaric nitrogen narcosis or the high pressure nervous syndrome (NSHP) produced by nitrogen or heliox gas mixtures under increased pressure was studied in mice and rabbit experiments with the use of pharmacological substances-analyzers. Accumulated data are indicative of lack of a significant role of the adrenergic system in the NSHP genesis and a protective effect of activation of the central but not peripheric adrenergic mediation in development of the behavioural and electrophysiological symptomatics of nitrogen narcosis. Mechanisms of NSHP and nitrogen narcosis and possible principles of pharmacological correction are under discussion.
Subject(s)
Adrenergic Agents/pharmacology , Central Nervous System/drug effects , High Pressure Neurological Syndrome/etiology , Inert Gas Narcosis/complications , Adrenergic alpha-Agonists/pharmacology , Adrenergic alpha-Antagonists/pharmacology , Adrenergic beta-Antagonists/pharmacology , Animals , Central Nervous System/physiopathology , Chinchilla , Dioxanes/pharmacology , Electroencephalography , Ephedrine/pharmacology , High Pressure Neurological Syndrome/drug therapy , High Pressure Neurological Syndrome/physiopathology , Inert Gas Narcosis/drug therapy , Inert Gas Narcosis/physiopathology , Male , Mice , Pressure/adverse effects , Propranolol/pharmacology , Rabbits , Signal TransductionABSTRACT
The effects of ethyl alcohol (1 ml/kg body weight), dextroamphetamine (15 mg), and nitrous oxide (20%) on reaction time were investigated in 6 subjects with a 2-, 3-, and 4-choice serial reaction time task. Each drug was assessed separately and in combination with nitrous oxide. The error rate was held constant. Neither ethanol and nitrous oxide nor amphetamine and nitrous oxide influenced the slope of the Hick-Hyman function, but the former combination increased the intercept while the latter decreased it. The drugs, either alone or in combination, shifted the frequency distributions of the reaction times as a whole, rather than modifying either their shapes or the pattern of the response latencies around an error. These results indicate that the drugs have a common pattern of effects on reaction time and that alcohol exacerbates narcosis while amphetamine ameliorates it. This is interpreted as support for the view that narcosis causes a nonspecific slowing of information processing by decreasing arousal.
Subject(s)
Amphetamine/pharmacology , Ethanol/pharmacology , Inert Gas Narcosis , Nitrous Oxide , Adult , Drug Therapy, Combination , Female , Humans , Inert Gas Narcosis/drug therapy , Male , Reaction TimeABSTRACT
The effect of either 10, 8, or 6 meq/kg of intraperitoneal lithium chloride or sodium chloride on the loss of righting response (RR50) produced by 18.2 ATA N2-ATA O2 was examined in rats. Results were compared to the effects of 10, 8, 6, or 4 meq/kg of intraperitoneal lithium chloride given 24 h before determination of the convulsion pressure (PC) in 40 rats compressed with He-O2 at 160 atm/h at 37 +/- 0.5 degrees C. Lithium (10 meq/kg) prevented the nitrogen-narcosis-induced loss of righting response but significantly potentiated the pressure (depth) at which convulsions and tremors occurred.
