phalloidine and Carbon-Tetrachloride-Poisoning

Topics: Animals; Calcium; Carbon Tetrachloride Poisoning; Cell Membrane Permeability; Cell Survival; Cells, Cultured; Galactosamine; Humans; Liver; Macrophages; Phalloidine; Time Factors

For the study of structure-activity relationships, the antihepatotoxic wedelolactone (7-methoxy-5,11,12-trihydroxy-coumestan) and 6 coumestan derivatives were synthesized by the application of a modified method of Wanzlich. An evaluation of the biological characteristics of the synthetic compounds and acuminatin from Musa acuminata showed that most of the wedelolactone derivatives significantly protected primary cultured liver cells from the toxicity of CCl4, galactosamine (Galc), and phalloidin, and strongly inhibited the activity of 5-lipoxygenase in porcine leukocytes. The hepatocyte protective activity was dependent on the C-7 substitution with pharmacological efficacy decreasing in the following order: EtO greater than MeO greater than OH greater than CH3(CH2)9. In addition, a free OH at C-5 of the wedelolactone molecule was shown to be important in protecting hepatocytes from CCl4 and Galc damage. Similar observation regarding the effect of C-7 substitution in wedelolactone was obtained in the 5-lipoxygenase test. In general, an increase in the lipophilicity in ring A increased the inhibition of 5-lipoxygenase activity. The synthetic wedelolactone was also found to have stimulatory effect on the RNA synthesis in isolated nuclei from hepatocytes.

Topics: Alanine Transaminase; Animals; Anti-Inflammatory Agents; Arachidonate Lipoxygenases; Carbon Tetrachloride Poisoning; Cell Survival; Chemical and Drug Induced Liver Injury; Coumarins; In Vitro Techniques; Leukocytes; Lipoxygenase Inhibitors; Liver; Phalloidine; Rats; RNA; Swine

The aim of the present study is to investigate the capacity of damaged rat liver cells to respond to a second inflammation by a change in plasma protein profile, while the first inflammatory process is in progress. Quantitation of these effects would be useful, especially in situations where patients are suffering from complications due to emergence of a new pathological factor. We therefore studied the effect of phalloidin on rat livers already made necrotic by oral intubation of CCl4. Our data showed that a decrease in acute-phase response does not necessarily always imply healing, but may also be indicative of a second pathological complication.

Topics: Amanitins; Animals; Blood Proteins; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; DNA; Immunoelectrophoresis; Liver; Phalloidine; Rats; Rats, Inbred Strains; Thymidine; Time Factors

Isolated hepatocytes, prepared from 5 day old rats, from regenerating livers of from livers after poisoning with carbon tetrachloride, are less sensitive to phalloidin in vitro than hepatocytes from untreated adult controls. The time course of the reduced susceptibility to phalloidin was compared with the ability of hepatocytes to take up bile acids under various conditions. SDS-electrophoresis of cell lysates gave no evidence for decreased levels of actin in cells with reduced sensitivity to phalloidin. In contrast, there was a good relationship between the active uptake of bile acids and the sensitivity of hepatocytes to phalloidin. The decreased response of hepatocytes from baby rats, from regenerating livers or from poisoned livers to phalloidin is more probably related to differences in phalloidin uptake than to a reduced endowment with microfilamentous structures.

Topics: Actins; Age Factors; Animals; Animals, Newborn; Bile Acids and Salts; Carbon Tetrachloride Poisoning; Cells; Chemical and Drug Induced Liver Injury; Liver Regeneration; Myosins; Oligopeptides; Phalloidine; Proteins; Rats

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.

Topics: Acetaminophen; Administration, Oral; Alanine Transaminase; Alcoholic Intoxication; Amanitins; Aniline Hydroxylase; Animals; Aspartate Aminotransferases; Bromobenzenes; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Ethanol; Galactosamine; Glutathione; Humans; L-Iditol 2-Dehydrogenase; Liver; Male; Mice; Microsomes, Liver; Organ Size; Phalloidine; Praseodymium; Thioacetamide

Topics: Adolescent; Adult; Aged; Animals; Bile; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Female; Flavonoids; Hepatitis; Hepatitis B; Humans; Liver; Liver Cirrhosis; Liver Diseases; Liver Function Tests; Male; Middle Aged; Phalloidine; Rabbits; Silymarin

Topics: Alanine Transaminase; Alcohol Oxidoreductases; Amanitins; Anesthetics, Local; Animals; Aspartate Aminotransferases; Body Temperature; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Dogs; Female; Flavonoids; L-Lactate Dehydrogenase; Lethal Dose 50; Male; Mice; Phalloidine; Rabbits; Rats; Silymarin; Sorbitol; Time Factors; Vascular Resistance