ABSTRACT
Silybin 11-O-phosphate 3 was synthesized by selective phosphorylation of silybin with POCl3. The pharmacological activity of 3 was evaluated in the rat by using the praseodymium poisoning test. Preliminary results showed that the compound possesses antihepatotoxic activity, possibly with lower potency compared to the reference drug silybin hemisuccinate.
Subject(s)
Chemical and Drug Induced Liver Injury/drug therapy , Organophosphates/chemical synthesis , Silymarin/analogs & derivatives , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Chemical and Drug Induced Liver Injury/blood , Chemical and Drug Induced Liver Injury/pathology , Liver/pathology , Magnetic Resonance Spectroscopy , Male , Organ Size , Organophosphates/pharmacology , Praseodymium/poisoning , Rats , Rats, Wistar , Silybin , Silymarin/chemical synthesis , Silymarin/pharmacology , Spectrophotometry, Infrared , Spectrophotometry, UltravioletABSTRACT
The hepatotoxic effects of carbon tetrachloride (0.01 ml/kg i.p.), thioacetamide (50 mg/kg intraperitoneally), paracetamol (0.5 g/kg intraperitoneally), and allyl alcohol (0.05 ml/kg intraperitoneally) as estimated by determination of serum enzyme activities (GOT, GPT, SDH) were enhanced in mice treated with one oral dose of 4.8 g/kg ethanol 16 hrs. previously. Pretreatment of mice with ethanol did not increase the hepatotoxic actions of bromobenzene (0.25 ml/kg intraperitoneally), phalloidin (1.5 mg/kg intraperitoneally), alpha-amanitin (0.75 mg/kg intraperitoneally), and praseodymium (12 mg/kg intravenously) though there was a trend to higher enzyme activities in the case of bromobenzene. In guinea-pigs ethanol also aggravated CCl4-induced liver damage, but only strengthened the hepatotoxic activity of D-galactosamine (150 mg/kg intraperitoneally). Treatment with 4.8 g/kg ethanol did not influence liver glutathione levels in mice but increased aniline hydroxylation in the 9000 x g liver homogenate supernatant of mice and guinea-pigs. A dose of 2.4 g/kg ethanol, on the other hand, neither increased aniline hydroxylase activity nor enhanced carbon tetrachloride-induced hepatotoxicity in mice. It is assumed that the enhanced sensitivity to hepatotoxic agents after treatment with ethanol may be due to an enhanced microsomal activation of these substances.
Subject(s)
Chemical and Drug Induced Liver Injury , Ethanol/pharmacology , Liver/drug effects , Acetaminophen/poisoning , Administration, Oral , Alanine Transaminase/blood , Alcoholic Intoxication , Amanitins/poisoning , Aniline Hydroxylase/metabolism , Animals , Aspartate Aminotransferases/blood , Bromobenzenes/poisoning , Carbon Tetrachloride Poisoning , Ethanol/administration & dosage , Galactosamine/poisoning , Glutathione/metabolism , Humans , L-Iditol 2-Dehydrogenase/blood , Liver/metabolism , Male , Mice , Microsomes, Liver/enzymology , Organ Size/drug effects , Phalloidine/poisoning , Praseodymium/poisoning , Thioacetamide/poisoningABSTRACT
Serum ornithine carbamoyltransferase (OCT) in rats poisoned with lanthanum, cerium and praseodymium. Acta Physiol. Pol., 1977, 28 (6): 589-594. The serum ornithine carbamoyltransferase in relation to doses of lanthanum, cerium and praseodymium, administered intravenously as chlorides, was investigated. A directly proportional relationship was found between the doses of these compounds and the serum enzyme level in rats. The lowest doses at which a rise in the serum OCT level occured were determined. They were: lanthanum - 0.75 mg/kg of body weight, cerium - 1.5 mg/kg, and praseodymium - 3 mh/kg. A decreasing toxicity of these elements with increasing value of atomic number was observed.
Subject(s)
Metals, Rare Earth/poisoning , Ornithine Carbamoyltransferase/blood , Animals , Cerium/poisoning , Female , Lanthanum/poisoning , Praseodymium/poisoning , RatsABSTRACT
After acute intoxication with praseodymium nitrate (10 mg/kg body weight i.v.), time functions of enzyme activities of GOT, GPT, ChE, AP and of free fatty acids concentration in rat serum were analysed and the results subjected to significance and correlation analysis. Time functions of free fatty acids concentration corresponded with those of enzyme activities of GOT and GPT. In the early state of intoxication serum concentrations of palmitoleinic and oleic acid were more increased than those of stearinic acid. There seems to be an alteration in the correlations of analysed measures with regard to their temporal changes parallel to the progress of intoxication.
