heliotrine and Chemical-and-Drug-Induced-Liver-Injury

Experimental pyrrolizidine alkaloid intoxication was produced in inbred Swiss mice. Animals were fed diets containing 0, 1, 3, 5, or 10% Heliotropium dolosum seed for 24 w. The seeds contained 0.13% total alkaloid concentration composed of 4 specific components: lasiocarpine (78.79%), heliosupine (11.96%), echimidine (5.43%), and heliotrine (3.82%). Deaths occurred in all dosed groups and increased with dietary seed concentration. Massive to submassive liver necrosis together with sinusoidal congestion, and hemorrhage or multifocal hepatocytic necrosis was limited to animals which survived < 5 w and were fed on 10% seed. Moderate to severe hepatomegalocytosis, scattered single cell necrosis, and mild subcapsuler fibrosis were seen in all test group animals that survived > 5 w. Intranuclear eosinophilic inclusions in hepatocytes and bile duct and ductular cell hyperplasia were the most noticeable lesions in the 1, 3, and 5% groups. There was mild to moderate renal tubular megalocytosis in the 3, 5, and 10% groups. It seems likely that H dolosum seed, at least to a limited extent, constitutes a health hazard for certain animal species.

Topics: Animals; Cell Nucleus; Chemical and Drug Induced Liver Injury; Diet; Dose-Response Relationship, Drug; Gas Chromatography-Mass Spectrometry; Hepatocytes; Kidney; Liver; Longevity; Male; Mice; Necrosis; Plant Poisoning; Plants, Toxic; Pyrrolizidine Alkaloids; Seeds

Antioxidant properties of yantocine, a preparation derived from Alhagi pseudalhagi Desy, were studied on a model of acute toxic hepatitis induced in random bred young male albino rats (90-100 g). Two experimental models were used: acute geliotrine hepatitis and acute CCl4 hepatitis. Yantocine was added to preparations of damaged plasma membranes (PM) in ascending doses. The results indicate that the level of malonic dialdehyde in the rat liver PM depended on the drug dose in both models of hepatitis. Linear dependence was observed for doses of 1.0-5.0 gamma. The capacity of yantocine to decrease the production of lipid peroxided was confirmed in vivo. After 3-day treatment with yantocine the level of lipid peroxides decreased by 15 and 12%, respectively, while the content of total phospholipids increased negligibly.

Topics: Animals; Carbon Tetrachloride Poisoning; Cell Membrane; Chemical and Drug Induced Liver Injury; Lipid Peroxidation; Liver; Male; Membrane Lipids; Phytotherapy; Plant Preparations; Pyrrolizidine Alkaloids; Rats

Acute hepatitis induced by heliotrine is accompanied by uncoupling of oxidative phosphorylation in liver mitochondria. The rate of oxygen uptake during succinate oxidation increased in all metabolic states, while the respiratory control index decreased by 45% because of the greater increase in the respiration rate in state 4 by comparison with that in state 3. Heliotrine poisoning also halved the rate of oxygen uptake in rat liver homogenates in the presence of ascorbate and tetramethylene-p-phenylenediamine. This is indicative of a lowering of cytochrome oxidase activity and of energy metabolism disturbances in rat liver. Preparations of cotton phosphatidylcholine (PC), both purified and as ATP-containing complexes (PC+ATP), as well as ATP alone, reduced the metabolic disorders in liver mitochondria of rats with acute heliotrine-induced hepatitis. The therapeutic effect of these preparations consisted in the restoration of oxidative phosphorylation coupling and of the cytochrome oxidase activity. The effect of PC+ATP was much greater than either PC or ATP alone. In contrast, the commercial preparation, Essential, had no beneficial effect.

Topics: Adenosine Triphosphate; Animals; Chemical and Drug Induced Liver Injury; Drug Synergism; Electron Transport Complex IV; Male; Mitochondria, Liver; Oxidative Phosphorylation; Phosphatidylcholines; Pyrrolizidine Alkaloids; Rats

Hepatocyte membranes destruction in experimental toxic hepatitis caused by heliotrine administration was accompanied by a 10-fold increase in blood serum activity of aldolase fructose-I-monophosphate, a decrease in cytochrome P-450 content, an increase in the rate of cytochrome P-450 inactivation, as well as a decrease in microsomal glucose-6-phosphatase activity. Administration of phosphatidylcholine liposomes decreased the activity of aldolase twofold, which indirectly shows partial reconstitution of liver cell membranes. Phosphatidylcholine protective action is also manifested in an increase in the activity of glucose-6-phosphatase, a microsomal marker enzyme, up to its control level and in a 20% reduced rate of cytochrome P-450 inactivation. It has been shown that destroyed liver cell membranes may be repaired by the introduction of phosphatidylcholine in the form of multilayer liposomes.

Topics: Animals; Cell Membrane; Chemical and Drug Induced Liver Injury; Cytochrome P-450 Enzyme System; Enzyme Activation; Fructose-Bisphosphate Aldolase; Glucose-6-Phosphatase; Liposomes; Male; Microsomes, Liver; Phosphatidylcholines; Pyrrolizidine Alkaloids; Rats

Topics: Adolescent; Adult; Alanine Transaminase; Animals; Aspartate Aminotransferases; Autoimmune Diseases; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Glucocorticoids; Hepatitis B; Humans; Hypersensitivity; Middle Aged; Pyrrolizidine Alkaloids; Rats